The classic infantile form of Niemann-Pick Disease, caused by mutation in SPHINGOMYELIN PHOSPHODIESTERASE. It is characterized by accumulation of SPHINGOMYELINS in the cells of the MONONUCLEAR PHAGOCYTE SYSTEM and other cell throughout the body leading to cell death. Clinical signs include JAUNDICE, hepatosplenomegaly, and severe brain damage.
A rare form of DEMENTIA that is sometimes familial. Clinical features include APHASIA; APRAXIA; CONFUSION; ANOMIA; memory loss; and personality deterioration. This pattern is consistent with the pathologic findings of circumscribed atrophy of the poles of the FRONTAL LOBE and TEMPORAL LOBE. Neuronal loss is maximal in the HIPPOCAMPUS, entorhinal cortex, and AMYGDALA. Some ballooned cortical neurons contain argentophylic (Pick) bodies. (From Brain Pathol 1998 Apr;8(2):339-54; Adams et al., Principles of Neurology, 6th ed, pp1057-9)
An autosomal recessive lipid storage disorder that is characterized by accumulation of CHOLESTEROL and SPHINGOMYELINS in cells of the VISCERA and the CENTRAL NERVOUS SYSTEM. Type C (or C1) and type D are allelic disorders caused by mutation of gene (NPC1) encoding a protein that mediate intracellular cholesterol transport from lysosomes. Clinical signs include hepatosplenomegaly and chronic neurological symptoms. Type D is a variant in people with a Nova Scotia ancestry.
A group of autosomal recessive disorders in which harmful quantities of lipids accumulate in the viscera and the central nervous system. They can be caused by deficiencies of enzyme activities (SPHINGOMYELIN PHOSPHODIESTERASE) or defects in intracellular transport, resulting in the accumulation of SPHINGOMYELINS and CHOLESTEROL. There are various subtypes based on their clinical and genetic differences.
An alpha-glucosidase inhibitor with antiviral action. Derivatives of deoxynojirimycin may have anti-HIV activity.
The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.
Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).
A complex of polyene antibiotics obtained from Streptomyces filipinensis. Filipin III alters membrane function by interfering with membrane sterols, inhibits mitochondrial respiration, and is proposed as an antifungal agent. Filipins I, II, and IV are less important.
An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.
Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.
A degenerative disease of the central nervous system characterized by balance difficulties; OCULAR MOTILITY DISORDERS (supranuclear ophthalmoplegia); DYSARTHRIA; swallowing difficulties; and axial DYSTONIA. Onset is usually in the fifth decade and disease progression occurs over several years. Pathologic findings include neurofibrillary degeneration and neuronal loss in the dorsal MESENCEPHALON; SUBTHALAMIC NUCLEUS; RED NUCLEUS; pallidum; dentate nucleus; and vestibular nuclei. (From Adams et al., Principles of Neurology, 6th ed, pp1076-7)
A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)
Transport proteins that carry specific substances in the blood or across cell membranes.
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4)
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
An autosomal recessive metabolic disorder due to deficient expression of amylo-1,6-glucosidase (one part of the glycogen debranching enzyme system). The clinical course of the disease is similar to that of glycogen storage disease type I, but milder. Massive hepatomegaly, which is present in young children, diminishes and occasionally disappears with age. Levels of glycogen with short outer branches are elevated in muscle, liver, and erythrocytes. Six subgroups have been identified, with subgroups Type IIIa and Type IIIb being the most prevalent.
Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.

Endogenous neuroprotective factors: neurosteroids. (1/138)

Neurosteroids are a group of steroid hormones synthesized by the brain in the presence of steroidogenic enzymes. Specific neurosteroids modulate function of several receptors, and also regulate growth of neurons, myelinization and synaptogenesis in the central nervous system. Some neurosteroids have been shown to display neuroprotective properties, which may have important implications for their potential use in the treatment of various neuropathologies such as: age-dependent dementia, stroke, epilepsy, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease (PD) and Niemann-Pick type C disease (NP-C). This paper focuses on neuroprotection afforded by neurosteroids.  (+info)

The adult form of Niemann-Pick disease type C. (2/138)

Niemann-Pick disease type C (NPC) is a fatal neurovisceral lipid storage disease of autosomal inheritance resulting from mutations in either the NPC1 (95% of families) or NPC2 gene. The encoded proteins appear to be involved in lysosomal/late endosomal transport of cholesterol, glycolipids and other molecules but their exact function is still unknown. The clinical spectrum of the disease ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. Based upon a comprehensive study of 13 unrelated adult patients diagnosed in France over the past 20 years as well as the analysis of the 55 other cases published since 1969, we have attempted to delineate the major clinical, radiological, biochemical and genotypic characteristics of adult NPC. Overall, mean age at onset (+/-SD) of neuropsychiatric symptoms was 25 +/- 9.7 years. The diagnosis of NPC was established after a mean delay of 6.2 +/- 6.4 years and the mean age at death (calculated from 20 cases) was 38 +/- 10.2 years. Major clinical features included cerebellar ataxia (76%), vertical supranuclear ophthalmoplegia (VSO, 75%), dysarthria, (63%), cognitive troubles (61%), movement disorders (58%), splenomegaly (54%), psychiatric disorders (45%) and dysphagia (37%). Less frequent signs were epilepsy and cataplexy. During the course of the disease, clinical features could be subdivided into (i) visceral signs (hepatomegaly or splenomegaly), (ii) cortical signs (psychiatric cognitive disorders and epilepsy); and (iii) deep brain signs (VSO, ataxia, movement disorders, dysarthria, dysphagia, cataplexy) which exhibited different evolution patterns. Asymptomatic and non-evolutive visceral signs were often noticed since early childhood (38.5% of our patients), followed by mild cortical signs in childhood (learning difficulties) and early adulthood (62% of cases among which 38% were psychiatric disorders). Deep brain signs were observed in 96% of patients and were usually responsible for death. In general, there was a good correlation between clinical signs and the localization of brain atrophy on MRI. The 'variant' biochemical phenotype characterized by mild abnormalities of the cellular trafficking of endocytosed cholesterol was over-represented in the adult form of NPC and seemed associated with less frequent splenomegaly in childhood and lesser psychiatric signs. Involvement of the NPC1 gene was shown in 33 families and of the NPC2 gene in one. Improving the knowledge of the disease among psychiatrists and neurologists appears essential since emerging treatments should be more efficient at the visceral or cognitive/psychiatric stages of the disease, before the occurrence of widespread deep brain neurological lesions.  (+info)

Lipid homeostasis and lipoprotein secretion in Niemann-Pick C1-deficient hepatocytes. (3/138)

Niemann-Pick C (NPC) disease is a fatal inherited disorder characterized by an accumulation of cholesterol and other lipids in late endosomes/lysosomes. Although this disease is considered to be primarily a neurodegenerative disorder, many NPC patients suffer from liver disease. We have investigated alterations that occur in hepatic lipid homeostasis using primary hepatocytes isolated from NPC1-deficient mice. The cholesterol content of Npc1(-/-) hepatocytes was 5-fold higher than that of Npc1(+/+) hepatocytes; phospholipids and cholesteryl esters also accumulated. In contrast, the triacylglycerol content of Npc1(-/-) hepatocytes was 50% lower than of Npc1(+/+) hepatocytes. We hypothesized that the cholesterol sequestration induced by NPC1 deficiency might inhibit very low density lipoprotein secretion. However, this process was enhanced by NPC1 deficiency and the secreted particles were enriched in cholesteryl esters. We investigated the mechanisms responsible for these changes. The synthesis of phosphatidylcholine, cholesteryl esters, and cholesterol in hepatocytes was increased by NPC1 deficiency and the amount of the mature form of sterol response element-binding protein-1 was also increased. These observations indicate that the enhanced secretion of lipoproteins from NPC1-deficient hepatocytes is due, at least in part, to increased lipid synthesis.  (+info)

Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling. (4/138)

Cholesterol is a prominent component of nerve terminals. To examine cholesterol's role in central neurotransmission, we treated hippocampal cultures with methyl-beta-cyclodextrin, which reversibly binds cholesterol, or mevastatin, an inhibitor of cholesterol biosynthesis, to deplete cholesterol. We also used hippocampal cultures from Niemann-Pick type C1-deficient mice defective in intracellular cholesterol trafficking. These conditions revealed an augmentation in spontaneous neurotransmission detected electrically and an increase in spontaneous vesicle endocytosis judged by horseradish peroxidase uptake after cholesterol depletion by methyl-beta-cyclodextrin. In contrast, responses evoked by action potentials and hypertonicity were severely impaired after the same treatments. The increase in spontaneous vesicle recycling and the decrease in evoked neurotransmission were reversible upon cholesterol addition. Cholesterol removal did not impact on the low level of evoked neurotransmission seen in the absence of synaptic vesicle SNARE protein synaptobrevin-2 whereas the increase in spontaneous fusion remained. These results suggest that synaptic cholesterol balances evoked and spontaneous neurotransmission by hindering spontaneous synaptic vesicle turnover and sustaining evoked exo-endocytosis.  (+info)

Clues to neuro-degeneration in Niemann-Pick type C disease from global gene expression profiling. (5/138)

BACKGROUND: Niemann-Pick Type C (NPC) disease is a neurodegenerative disease that is characterized by the accumulation of cholesterol and glycosphingolipids in the late endocytic pathway. The majority of NPC cases are due to mutations in the NPC1 gene. The precise function of this gene is not yet known. METHODOLOGY/PRINCIPAL FINDINGS: Using cDNA microarrays, we analyzed the genome-wide expression patterns of human fibroblasts homozygous for the I1061T NPC1 mutation that is characterized by a severe defect in the intracellular processing of low density lipoprotein-derived cholesterol. A distinct gene expression profile was identified in NPC fibroblasts from different individuals when compared with fibroblasts isolated from normal subjects. As expected, NPC1 mutant cells displayed an inappropriate homeostatic response to accumulated intracellular cholesterol. In addition, a number of striking parallels were observed between NPC disease and Alzheimer's disease. CONCLUSIONS/SIGNIFICANCE: Many genes involved in the trafficking and processing of amyloid precursor protein and the microtubule binding protein, tau, were more highly expressed. Numerous genes important for membrane traffic and the cellular regulation of calcium, metals and other ions were upregulated. Finally, NPC fibroblasts exhibited a gene expression profile indicative of oxidative stress. These changes are likely contributors to the pathophysiology of Niemann-Pick Type C disease.  (+info)

Defect in fatty acid esterification of dolichol in Niemann-Pick type C1 mouse livers in vivo. (6/138)

Fatty acid esterification of dolichol and cholesterol in Niemann-Pick type C1 mouse (Balb/c NIH npc1(-/-)) livers was investigated in response to treatment with peroxisomal proliferators. These inducers have hypolipidemic properties and influence the mevalonate pathway and the intracellular transport of the final products of this biosynthetic route. Such inducers are consequently interesting to use in a disease model with defective intracellular transport of lipids. In wild-type mice, the levels of dolichol and cholesterol found as free alcohols were not changed to any great extent upon treatment with the peroxisomal inducers dehydroepiandrosterone, clofibrate and diethylhexylphtalate. In contrast, the amounts of dolichyl esters increased whereas cholesteryl esters decreased by the same treatments. The rate of enzymatic esterification of dolichol in isolated microsomes was accordingly elevated after 5- to 7-day treatments with the efficient peroxisomal proliferators DEHP and PFOA, while the corresponding esterification of cholesterol was decreased. Upon peroxisomal induction in npc1(-/-) mice, the enzymatic dolichol esterification in vitro increased whereas the low concentration of dolichyl esters remained unchanged. The results thus demonstrate that the induction of fatty acid esterification of dolichol in vivo is impaired in npc1(-/-) mouse liver. It is therefore proposed that the intracellular lipid transport defect in npc1(-/-) mouse liver disables either dolichol and/or the fatty acid from reaching the site of esterification in vivo. This proposal was strengthened by the finding that the amount of dolichol was decreased in an isolated Golgi fraction from npc1(-/-) mice.  (+info)

Endosomal accumulation of Toll-like receptor 4 causes constitutive secretion of cytokines and activation of signal transducers and activators of transcription in Niemann-Pick disease type C (NPC) fibroblasts: a potential basis for glial cell activation in the NPC brain. (7/138)

Niemann-Pick disease type C (NPC) is an inherited lipid storage disorder caused by mutations in NPC1 or NPC2 genes. Loss of function of either protein results in the endosomal accumulation of cholesterol and other lipids, progressive neurodegeneration, and robust glial cell activation. Here, we report that cultured human NPC fibroblasts secrete interferon-beta, interleukin-6 (IL-6), and IL-8, and contain increased levels of signal transducers and activators of transcription (STATs). These cells also contained increased levels of Toll-like receptor 4 (TLR4) that accumulated in cholesterol-enriched endosomes/lysosomes, and small interfering RNA knockdown of this receptor reduced cytokine secretion. In the NPC1-/- mouse brain, glial cells expressed TLR4 and IL-6, whereas both glial and neuronal cells expressed STATs. Genetic deletion of TLR4 in NPC1-/- mice reduced IL-6 secretion by cultured fibroblasts but failed to alter STAT levels or glial cell activation in the brain. In contrast, genetic deletion of IL-6 normalized STAT levels and suppressed glial cell activation. These findings indicate that constitutive cytokine secretion leads to activation of STATs in NPC fibroblasts and that this secretion is partly caused by an endosomal accumulation of TLR4. These results also suggest that similar signaling events may underlie glial cell activation in the NPC1-/- mouse brain.  (+info)

Monocyte cholesterol homeostasis correlates with the presence of detergent resistant membrane microdomains. (8/138)

BACKGROUND: Lipid membrane microdomains are involved in the regulation of biological functions of monocyte membrane proteins. These microdomains show a relative resistance to non-ionic detergents providing an easy analytical tool to study them. METHODS: Here, we applied a rapid detergent-based flow cytometric assay to investigate microdomain association of proteins on monocytes from whole blood samples. The association of known surface antigens with detergent resistant fraction of membranes (DRMs) was compared using monocytes from healthy blood donors, patients with genetic disorders affecting cellular cholesterol traffic and patients with systemic inflammatory response. RESULTS: All investigated surface antigens of Niemann-Pick type C (NPC)-mutant monocytes with impaired cholesterol influx and defective late endosome cholesterol trafficking, presented a strongly increased DRM-association. Though, membrane antigens of ATP binding cassette transporter A1 (ABCA1)-mutant monocytes with impaired cholesterol efflux did not show alterations in DRM-association. Differential CD14-dependent receptor clustering within microdomains was also investigated in response to in vivo lipopolysaccharide (LPS) and/or atherogenic lipoprotein activation. Increased DRM-association of the GPI-anchored proteins CD14, CD55, the Fcgamma receptor CD64, the scavenger receptors CD36, CD91 and CD163, the integrin CD11a, and complement receptor 3 complex CD11b/CD18 were observed from patients with systemic inflammatory response syndrome (SIRS)/sepsis or coronary artery disease (CAD)/myocardial infarction. Interestingly, the tetraspanin CD81 presented increased DRM-association in SIRS/sepsis patients, but not in CAD patients. Moreover, the pentaspanin CD47 and the Fcgamma RIII CD16 showed an increased DRM partition in CAD patients but disassembled from DRMs in SIRS/sepsis patients. CONCLUSIONS: Our results demonstrate that flow cytometric analysis of short time in situ detergent extraction provides a powerful tool for rapid screening of blood monocyte DRMs to preselect patients with potential raft/microdomain abnormalities for more detailed analysis.  (+info)

Niemann-Pick Disease, Type A (NPD A) is a rare inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase (ASM). This enzyme defect results in the accumulation of lipids, particularly sphingomyelin and cholesterol, within various cells of the body, including brain cells, liver cells, and white blood cells.

The accumulation of these lipids leads to progressive damage to these organs, causing a range of symptoms such as an enlarged liver (hepatomegaly), anemia, jaundice, and neurological problems like developmental delay, seizures, loss of muscle tone, and difficulty with swallowing. NPD A is typically diagnosed in infancy or early childhood and is often fatal by around two to three years of age due to severe neurological complications. It is an autosomal recessive disorder, meaning that an individual must inherit two copies of the defective gene (one from each parent) to develop the condition.

Pick's disease, also known as Frontotemporal dementia (FTD), is a rare form of degenerative brain disorder that affects the frontal and temporal lobes of the brain. It is characterized by progressive shrinkage (atrophy) of these regions, resulting in a decline in cognitive abilities, behavioral changes, and language difficulties.

The medical definition of Pick's disease includes the following key features:

1. Progressive deterioration of cognitive functions, including memory, judgment, and problem-solving skills.
2. Changes in personality, emotional blunting, and loss of social inhibitions.
3. Language difficulties, such as difficulty with word finding, grammar, and comprehension.
4. Presence of abnormal protein deposits called Pick bodies or Pick cells in the affected brain regions.
5. Exclusion of other causes of dementia, such as Alzheimer's disease, vascular dementia, or Lewy body dementia.

Pick's disease typically affects people between the ages of 40 and 60, and it tends to progress more rapidly than other forms of dementia. Currently, there is no cure for Pick's disease, and treatment focuses on managing symptoms and improving quality of life.

Niemann-Pick Disease, Type C (NPC) is a rare, progressive, and fatal neurovisceral lipid storage disorder caused by mutations in the NPC1 or NPC2 genes. These genetic defects result in impaired intracellular transport of cholesterol and other lipids, leading to excessive accumulation within lysosomes of various tissues, particularly in the brain, liver, spleen, and lungs.

The disease primarily affects children, although late-onset forms have been reported in adults. The symptoms and severity can vary widely among patients but often include neurological manifestations such as ataxia, dysarthria, dysphagia, cognitive decline, seizures, and vertical supranuclear gaze palsy (VSGP). Other features may involve visceral involvement like hepatosplenomegaly, jaundice, or pulmonary complications.

There is currently no cure for NPC, but treatments aim to manage symptoms, slow disease progression, and improve quality of life. Miglustat and cyclodextrin (HPβCD) are two FDA-approved therapeutic options that have shown some promise in stabilizing or delaying neurological decline in NPC patients. Early diagnosis and intervention are crucial for optimizing outcomes and providing appropriate supportive care.

Niemann-Pick diseases are a group of inherited metabolic disorders characterized by the accumulation of lipids, particularly sphingomyelin and cholesterol, within cells due to deficiencies in certain enzymes. These diseases are caused by mutations in the SMPD1, NPC1, or NPC2 genes, among others. There are four main types of Niemann-Pick disease (Types A, B, C, and D), each with varying severity and symptoms.

Type A and Type B diseases, also known as Acid Sphingomyelinase Deficiency or ASMD, result from mutations in the SMPD1 gene leading to a deficiency of acid sphingomyelinase enzyme. This causes excessive accumulation of sphingomyelin in various tissues, particularly in the liver, spleen, lungs, and brain.

Type A is the most severe form, typically presenting in infancy with symptoms such as developmental delay, feeding difficulties, enlarged liver and spleen, lung infection, and progressive neurological degeneration, which often leads to early death, usually before age 3.

Type B has a broader range of severity and onset, from infancy to adulthood. Symptoms may include enlarged liver and spleen, lung disease, poor growth, and varying degrees of neurological impairment. Type B patients can survive into adolescence or adulthood, depending on the severity of their symptoms.

Type C and Type D diseases, also known as Niemann-Pick Type C Disease (NPC), are caused by mutations in either the NPC1 or NPC2 genes, leading to defective intracellular lipid transport. This results in excessive accumulation of cholesterol and other lipids within cells, particularly in the brain, liver, spleen, and lungs.

Type C typically presents in childhood but can also manifest in adolescence or adulthood. Symptoms include progressive neurological degeneration, ataxia, seizures, dementia, problems with speech and swallowing, and yellowish skin (jaundice) at birth or during infancy due to liver involvement. Type C patients usually have a shorter life expectancy, often surviving into their teens, twenties, or thirties.

Type D is a subtype of NPC that affects people of Nova Scotian descent and has similar symptoms to Type C but with an earlier onset and faster progression.

1-Deoxynojirimycin (DNJ) is an antagonist of the enzyme alpha-glucosidase, which is involved in the digestion of carbohydrates. DNJ is a naturally occurring compound found in some plants, including mulberry leaves and the roots of the African plant Moringa oleifera. It works by binding to the active site of alpha-glucosidase and inhibiting its activity, which can help to slow down the digestion and absorption of carbohydrates in the small intestine. This can help to reduce postprandial glucose levels (the spike in blood sugar that occurs after a meal) and may have potential benefits for the management of diabetes and other metabolic disorders. DNJ is also being studied for its potential anti-cancer effects.

Cholesterol is a type of lipid (fat) molecule that is an essential component of cell membranes and is also used to make certain hormones and vitamins in the body. It is produced by the liver and is also obtained from animal-derived foods such as meat, dairy products, and eggs.

Cholesterol does not mix with blood, so it is transported through the bloodstream by lipoproteins, which are particles made up of both lipids and proteins. There are two main types of lipoproteins that carry cholesterol: low-density lipoproteins (LDL), also known as "bad" cholesterol, and high-density lipoproteins (HDL), also known as "good" cholesterol.

High levels of LDL cholesterol in the blood can lead to a buildup of cholesterol in the walls of the arteries, increasing the risk of heart disease and stroke. On the other hand, high levels of HDL cholesterol are associated with a lower risk of these conditions because HDL helps remove LDL cholesterol from the bloodstream and transport it back to the liver for disposal.

It is important to maintain healthy levels of cholesterol through a balanced diet, regular exercise, and sometimes medication if necessary. Regular screening is also recommended to monitor cholesterol levels and prevent health complications.

Glycogen Storage Disease Type I (GSD I) is a rare inherited metabolic disorder caused by deficiency of the enzyme glucose-6-phosphatase, which is necessary for the liver to release glucose into the bloodstream. This leads to an accumulation of glycogen in the liver and abnormally low levels of glucose in the blood (hypoglycemia).

There are two main subtypes of GSD I: Type Ia and Type Ib. In Type Ia, there is a deficiency of both glucose-6-phosphatase enzyme activity in the liver, kidney, and intestine, leading to hepatomegaly (enlarged liver), hypoglycemia, lactic acidosis, hyperlipidemia, and growth retardation. Type Ib is characterized by a deficiency of glucose-6-phosphatase enzyme activity only in the neutrophils, leading to recurrent bacterial infections.

GSD I requires lifelong management with frequent feedings, high-carbohydrate diet, and avoidance of fasting to prevent hypoglycemia. In some cases, treatment with continuous cornstarch infusions or liver transplantation may be necessary.

Tau proteins are a type of microtubule-associated protein (MAP) found primarily in neurons of the central nervous system. They play a crucial role in maintaining the stability and structure of microtubules, which are essential components of the cell's cytoskeleton. Tau proteins bind to and stabilize microtubules, helping to regulate their assembly and disassembly.

In Alzheimer's disease and other neurodegenerative disorders known as tauopathies, tau proteins can become abnormally hyperphosphorylated, leading to the formation of insoluble aggregates called neurofibrillary tangles (NFTs) within neurons. These aggregates disrupt the normal function of microtubules and contribute to the degeneration and death of nerve cells, ultimately leading to cognitive decline and other symptoms associated with these disorders.

Filipin is not a medical term itself, but it is the name given to a group of compounds that are used in medicine and research. Medically, Filipin is often referred to as Filipin III or Filipin stain, which is a fluorescent polyene antibiotic used in the study of lipids, particularly in diagnosing certain types of lipid storage diseases such as Niemann-Pick disease type C. The Filipin stain binds to unesterified cholesterol and forms complexes that exhibit blue fluorescence under ultraviolet light. This property is used to detect the accumulation of free cholesterol in various tissues and cells, which can be indicative of certain diseases or conditions.

Dementia is a broad term that describes a decline in cognitive functioning, including memory, language, problem-solving, and judgment, severe enough to interfere with daily life. It is not a specific disease but rather a group of symptoms that may be caused by various underlying diseases or conditions. Alzheimer's disease is the most common cause of dementia, accounting for 60-80% of cases. Other causes include vascular dementia, Lewy body dementia, frontotemporal dementia, and Huntington's disease.

The symptoms of dementia can vary widely depending on the cause and the specific areas of the brain that are affected. However, common early signs of dementia may include:

* Memory loss that affects daily life
* Difficulty with familiar tasks
* Problems with language or communication
* Difficulty with visual and spatial abilities
* Misplacing things and unable to retrace steps
* Decreased or poor judgment
* Withdrawal from work or social activities
* Changes in mood or behavior

Dementia is a progressive condition, meaning that symptoms will gradually worsen over time. While there is currently no cure for dementia, early diagnosis and treatment can help slow the progression of the disease and improve quality of life for those affected.

Tauopathies are a group of neurodegenerative disorders that are characterized by the abnormal accumulation and aggregation of the microtubule-associated protein Tau in neurons and glial cells. These misfolded Tau proteins form insoluble inclusions, such as neurofibrillary tangles (NFTs) and neuropil threads, which are associated with the degeneration and loss of neurons in specific regions of the brain.

Tauopathies include several well-known diseases, such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia with Parkinsonism-17 (FTDP-17). The exact cause of Tauopathies remains unclear, but genetic mutations, environmental factors, or a combination of both may contribute to the development and progression of these disorders.

The accumulation of abnormal Tau aggregates is believed to play a central role in the neurodegenerative process, leading to cognitive decline, motor impairment, and other neurological symptoms associated with Tauopathies. The diagnosis of Tauopathies typically involves clinical evaluation, imaging studies, and sometimes postmortem examination of brain tissue. Currently, there are no effective disease-modifying treatments for Tauopathies, but ongoing research is focused on developing therapies that target Tau aggregation and clearance to slow down or halt the progression of these debilitating disorders.

Progressive Supranuclear Palsy (PSP) is a rare neurological disorder characterized by the progressive degeneration of brain cells that regulate movement, thoughts, behavior, and eye movements. The term "supranuclear" refers to the location of the damage in the brain, specifically above the level of the "nuclei" which are clusters of nerve cells that control voluntary movements.

The most common early symptom of PSP is a loss of balance and difficulty coordinating eye movements, particularly vertical gaze. Other symptoms may include stiffness or rigidity of muscles, slowness of movement, difficulty swallowing, changes in speech and writing, and cognitive decline leading to dementia.

PSP typically affects people over the age of 60, and its progression can vary from person to person. Currently, there is no cure for PSP, and treatment is focused on managing symptoms and maintaining quality of life.

Charcot-Marie-Tooth disease (CMT) is a group of inherited disorders that cause nerve damage, primarily affecting the peripheral nerves. These are the nerves that transmit signals between the brain and spinal cord to the rest of the body. CMT affects both motor and sensory nerves, leading to muscle weakness and atrophy, as well as numbness or tingling in the hands and feet.

The disease is named after the three physicians who first described it: Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth. CMT is characterized by its progressive nature, meaning symptoms typically worsen over time, although the rate of progression can vary significantly among individuals.

There are several types of CMT, classified based on their genetic causes and patterns of inheritance. The two most common forms are CMT1 and CMT2:

1. CMT1: This form is caused by mutations in the genes responsible for the myelin sheath, which insulates peripheral nerves and allows for efficient signal transmission. As a result, demyelination occurs, slowing down nerve impulses and causing muscle weakness, particularly in the lower limbs. Symptoms usually begin in childhood or adolescence and include foot drop, high arches, and hammertoes.
2. CMT2: This form is caused by mutations in the genes responsible for the axons, the nerve fibers that transmit signals within peripheral nerves. As a result, axonal degeneration occurs, leading to muscle weakness and atrophy. Symptoms usually begin in early adulthood and progress more slowly than CMT1. They primarily affect the lower limbs but can also involve the hands and arms.

Diagnosis of CMT typically involves a combination of clinical evaluation, family history, nerve conduction studies, and genetic testing. While there is no cure for CMT, treatment focuses on managing symptoms and maintaining mobility and function through physical therapy, bracing, orthopedic surgery, and pain management.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate) and die. It's the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently.

The early signs of the disease include forgetting recent events or conversations. As the disease progresses, a person with Alzheimer's disease will develop severe memory impairment and lose the ability to carry out everyday tasks.

Currently, there's no cure for Alzheimer's disease. However, treatments can temporarily slow the worsening of dementia symptoms and improve quality of life.

Glycogen Storage Disease Type II, also known as Pompe Disease, is a genetic disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). This enzyme is responsible for breaking down glycogen, a complex sugar that serves as energy storage, within lysosomes. When GAA is deficient, glycogen accumulates in various tissues, particularly in muscle cells, leading to their dysfunction and damage.

The severity of Pompe Disease can vary significantly, depending on the amount of functional enzyme activity remaining. The classic infantile-onset form presents within the first few months of life with severe muscle weakness, hypotonia, feeding difficulties, and respiratory insufficiency. This form is often fatal by 1-2 years of age if left untreated.

A later-onset form, which can present in childhood, adolescence, or adulthood, has a more variable clinical course. Affected individuals may experience progressive muscle weakness, respiratory insufficiency, and cardiomyopathy, although the severity and rate of progression are generally less pronounced than in the infantile-onset form.

Enzyme replacement therapy with recombinant human GAA is available for the treatment of Pompe Disease and has been shown to improve survival and motor function in affected individuals.

Lysosomes are membrane-bound organelles found in the cytoplasm of eukaryotic cells. They are responsible for breaking down and recycling various materials, such as waste products, foreign substances, and damaged cellular components, through a process called autophagy or phagocytosis. Lysosomes contain hydrolytic enzymes that can break down biomolecules like proteins, nucleic acids, lipids, and carbohydrates into their basic building blocks, which can then be reused by the cell. They play a crucial role in maintaining cellular homeostasis and are often referred to as the "garbage disposal system" of the cell.

Glycogen Storage Disease Type III, also known as Cori or Forbes disease, is a rare inherited metabolic disorder caused by deficiency of the debranching enzyme amylo-1,6-glucosidase, which is responsible for breaking down glycogen in the liver and muscles. This results in an abnormal accumulation of glycogen in these organs leading to its associated symptoms.

There are two main types: Type IIIa affects both the liver and muscles, while Type IIIb affects only the liver. Symptoms can include hepatomegaly (enlarged liver), hypoglycemia (low blood sugar), hyperlipidemia (high levels of fats in the blood), and growth retardation. In Type IIIa, muscle weakness and cardiac problems may also occur.

The diagnosis is usually made through biochemical tests and genetic analysis. Treatment often involves dietary management with frequent meals to prevent hypoglycemia, and in some cases, enzyme replacement therapy. However, there is no cure for this condition and life expectancy can be reduced depending on the severity of the symptoms.

Neurofibrillary tangles are a pathological hallmark of several neurodegenerative disorders, most notably Alzheimer's disease. They are intracellular inclusions composed of abnormally phosphorylated and aggregated tau protein, which forms paired helical filaments. These tangles accumulate within the neurons, leading to their dysfunction and eventual death. The presence and density of neurofibrillary tangles are strongly associated with cognitive decline and disease progression in Alzheimer's disease and other related dementias.

Niemann-Pick type C is biochemically, genetically and clinically distinct from Niemann-Pick Types A or and B. In Types A and B ... "eMedicine - Niemann-Pick Disease : Article by Robert A Schwartz". Retrieved 2008-10-27. "Niemann-Pick Disease". Retrieved 2008- ... November 2008). "Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium". ... including Niemann-Pick Disease Type C. The US FDA has granted IntraBio a Rare Pediatric Disease Designation for N-Acetyl- ...
... which includes types A and B Niemann-Pick disease type A: classic infantile Niemann-Pick disease type B: visceral Niemann-Pick ... Type C is the most common form of the disease Type C2 is a rare form of the disease. Niemann-Pick disease type D (or Nova ... Lysosomal storage disease Niemann-Pick disease, type C Gaucher's disease Medical genetics of Ashkenazi Jews "Niemann-Pick". ... "Niemann Pick Disease Type C". National Organization for Rare Disorders. "NIEMANN-PICK DISEASE, TYPE B". OMIM. 9 April 2019. ...
... refers to two different types of Niemann-Pick disease which are associated with the ... Children affected by Niemann Pick Type A rarely live beyond 18 months. Niemann-Pick Type A occurs more frequently among ... Online Mendelian Inheritance in Man (OMIM): Niemann-Pick Disease, Type B - 607616 (Articles with short description, Short ... Niemann-Pick Type A, the most common type, occurs in infants and is characterized by jaundice, an enlarged liver, failure to ...
Niemann-Pick Disease Type A, Niemann-Pick Disease Type B OMIM entries on Acid Sphingomyelinase Deficiency Overview of all the ... Levran O, Desnick RJ, Schuchman EH (September 1991). "Niemann-Pick type B disease. Identification of a single codon deletion in ... Schuchman EH (1996). "Two new mutations in the acid sphingomyelinase gene causing type a Niemann-pick disease: N389T and R441X ... a model of types A and B Niemann-Pick disease". Nature Genetics. 10 (3): 288-93. doi:10.1038/ng0795-288. PMID 7670466. S2CID ...
These include the following: Prader-Willi syndrome; Norrie disease; Niemann-Pick disease, type C; and myotonic dystrophy. ... Celiac disease is another autoimmune disease associated with poor sleep quality (which may lead to hypersomnia), "not only at ... Also, neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, or multiple system atrophy are frequently ... Neuromuscular diseases and spinal cord diseases often lead to sleep disturbances due to respiratory dysfunction causing sleep ...
... and the chaperone therapy for Fabry disease, ERT for Niemann-Pick disease type B, and the RNA Interference Therapy for the ... cross-sectional survey study of the natural history of Niemann-Pick disease Type B. Pediatrics 122: e341-349, 2008. doi:10.1542 ... Acid sphingomyelinase protein and methods of treating type B Niemann-Pick disease, (2003). Method for enhancing mutant enzyme ... "Acid sphingomyelinase protein and methods of treating type B Niemann-Pick disease", published 2003-04-01, assigned to Mount ...
cite book}}: ,work= ignored (help) Evans, WRH; Hendriksz, CJ (2017). "Niemann-Pick type C disease - the tip of the iceberg? A ... Niemann-Pick diseases Osteoarthritis Osteoporosis Parkinson's disease Pulmonary arterial hypertension All prion diseases ( ... Alzheimer's disease (AD) Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) Cancers Charcot-Marie-Tooth disease (CMT) ... coronary artery disease) and neoplastic diseases (e.g. cancers). Many degenerative diseases exist and some are related to aging ...
"Sea-blue histiocytosis secondary to Niemann-Pick disease type B: a case report". Ann. Hematol. 80 (10): 620-2. doi:10.1007/ ... Suzuki O, Abe M (April 2007). "Secondary sea-blue histiocytosis derived from Niemann-Pick disease". J Clin Exp Hematop. 47 (1 ... 2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. Faivre L, Saugier-Veber ...
... can cause serious issues that lead to Niemann-Pick disease, type C. Niemann-Pick disease, type C is a rare disorder that ... type C, which is one of the 3 types of the Niemann-Pick diseases(Type A,B, and C). This disease can lead to an over ... "Niemann Pick Disease Type C". NORD (National Organization for Rare Disorders). Retrieved 2022-04-28. Vanier MT, Millat G ( ... Epididymal secretory protein E1 is a protein associated with Niemann-Pick disease, ...
FDA Advisory Briefing Book for Miglustat (Ogt 918, Zavesca) in Niemann-Pick Type C Disease NDA 021-348/S-007 Archived 9 May ... 23 March 2010 Zavesca (Miglustat) First Treatment Available in Canada for Rare Progressive Niemann-Pick Type C Disease Archived ... December 2020). "Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1". JAMA Neurology. 77 (12): ... and Japan for treating progressive neurological complications in people with Niemann-Pick disease, type C (NPC). On 26 April ...
... also known as Niemann-Pick C2 protein), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary ... "Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease". Proc. Natl. Acad. Sci. U.S.A. 100 (5): ... disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes. House dust mite allergen ...
IntraBio is also conducting parallel clinical trials with N-Acetyl-L-Leucine for the treatment of Niemann-Pick disease type C ... "N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC)". clinicaltrials.gov. Retrieved 2019-08-01. "N-Acetyl-L-Leucine for ... Tay-Sachs disease, AB variant, and Sandhoff disease might easily have been defined together as a single disease, because the ... The diseases are better known by their individual names: Tay-Sachs disease, AB variant, and Sandhoff disease. Beta- ...
The preclinical pipeline includes programs for Niemann Pick Type C, Parkinson's, Tay-Sachs disease. The early development ... In 2018, for its commitment to achieving medical advances for the benefit of patients with orphan diseases and its exponential ... "Phase IIA, Double-blind, Randomized, Placebo-controlled Study of the Efficacy and Safety of SOM3355 in Huntington's Disease (HD ... SOM Biotech's clinical pipeline includes programs for TTR Amyloidosis, chorea in Huntington's disease, Phenylketonuria, COVID- ...
Niemann-Pick Disease, Type C, or envenomation such as from a scorpion sting. The location of the lesion determines the type of ... Other conditions such as Niemann-Pick disease type C have limited drug therapeutic options. Stroke victims with conjugate gaze ... Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease ... One other type of gaze palsy is a horizontal saccadic palsy. Saccades are very quick intermittent eye movements. The paramedian ...
Morbidity and mortality in type B Niemann-Pick disease. Genet Med 2013;15:618-623. Cassiman D, Packman S, Bembi B, et al. Cause ... The main members of this group are Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay-Sachs disease and ... Niemann-Pick disease type B presenting with hepatosplenomegaly and thrombocytopenia. South Med J. 2008 Nov;101(11):1188. doi: ... ISBN 0-7817-8624-X. Niemann-Pick disease from Genetics Home Reference. Reviewed: January 2008. Based on an incidence in a ...
... disease signs and symptoms in children). Historically referred to as Niemann-Pick disease types A (NPD A) and B (NPD B), ASMD ... "First therapy to treat two types of Niemann-Pick disease, a rare genetic metabolic disorder". European Medicines Agency (EMA) ( ... 2022). "Atherogenic lipid profile in patients with Niemann-Pick disease type B: What treatment strategies?". J Clin Lipidol. 16 ... type A/B or type B. Xenpozyme was reviewed under the accelerated assessment program of the European Medicines Agency (EMA). The ...
Niemann-Pick disease type C, another lipid storage disease, includes abnormal lipid storage in sweat glands. Schindler disease ... Elleder, M.; Jirásek, A.; Smíd, F. (19 December 1975). "Niemann-Pick disease (Crocker's type C): A histological study of the ... Some diseases of the sweat glands include: Fox-Fordyce disease The apocrine sweat glands become inflamed, causing a persistent ... Kearns-Sayre syndrome, a disease of the mitochondria, involves abnormal mitochondria in eccrine sweat glands. Lafora disease is ...
July 1997). "Linkage of Niemann-Pick disease type D to the same region of human chromosome 18 as Niemann-Pick disease type C". ... results in Niemann-Pick disease, type C. Niemann-Pick disease, type C is a rare neurovisceral lipid storage disorder resulting ... "Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann- Pick type C disease ... "Entrez Gene: NPC1 Niemann-Pick disease, type C1". Carstea ED, Polymeropoulos MH, Parker CC, Detera-Wadleigh SD, O'Neill RR, ...
This is termed Hb Barts (consists of y-4 tetramers). Uncommonly, Niemann-Pick disease Type C (NPC) and Gaucher disease type 2 ... Rh disease is a hemolytic disease of newborns. Pregnant mothers do not always have the same blood type as their child. During ... This enzyme deficiency is the cause of the lysosomal storage disease called mucopolysaccharidosis type VII. Congenital ... Due to preventative methods developed in the 1970s, the incidence of Rh disease has markedly declined. Rh disease can be ...
Niemann-Pick disease type C, GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases), and ataxia-telangiectasia. In 2020, IntraBio ... "N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC) - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved ... Reports Further Detail on Positive Data from IB1001 Multinational Clinical Trial for the Treatment of Niemann-Pick disease Type ... announced the successful multinational clinical trial results of the Niemann-Pick type C clinical trial. IntraBio is also ...
Brady and his colleagues identified the enzymatic defects in Gaucher's disease, Niemann-Pick disease, Fabry disease and the ... Infantile Type II Gaucher's disease: in utero diagnosis and fetal pathology. J Pediatr 1972; 81: 1134-1139. Brady RO, Pentchev ... Kampine JP, Brady RO, Kanfer JN, Feld M, Shapiro D. The diagnosis of Gaucher's disease and Niemann-Pick disease using small ... Epstein CJ, Brady RO, Schneider EL, Bradley RM, Shapiro D. In utero diagnosis of Niemann-Pick disease. Am J Hum Genet 1971; 23 ...
"Molecular cloning of the mouse apolipoprotein D gene and its upregulated expression in Niemann-Pick disease type C mouse model ... Niemann-Pick type C (NPC) is a genetic disorder affecting cholesterol transport that is accompanied by chronic progressive ... hippocampus and cortex of human patients with Alzheimer's disease, cerebrovascular disease, motoneuron disease, ... involved in several pathologies such as cancer and Alzheimer's disease. Studies on several cell types have shown that ApoD ...
"Chronic administration of an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C disease in a mouse model ... Recent evidence also suggests vorinostat can be a therapeutic tool for Niemann-Pick type C1 (NPC1), a rare lysosomal lipid ... Vorinostat has also been used to treat Sézary syndrome, another type of lymphoma closely related to CTCL. A recent study ... when the disease persists, gets worse, or comes back during or after two systemic therapies. The compound was developed by ...
PTCH1 has homology to Niemann-Pick disease, type C1 (NPC1) that is known to transport lipophilic molecules across a membrane. ... Davies JP, Chen FW, Ioannou YA (December 2000). "Transmembrane molecular pump activity of Niemann-Pick C1 protein". Science. ... There are three proposed mechanisms of aberrant Hh signaling activation in different cancer types: Type I involves ligand- ... Diseases associated with the malfunction of this pathway include cancer. The Hedgehog signaling pathway is one of the key ...
The lysosomal storage disorders Niemann-Pick disease, SMPD1-associated (Type A and B) are characterized by a deficiencies in ... Schuchman, Edward H (May 2010). "Acid Sphingomyelinase, cell membranes and human disease: Lessons from Niemann-Pick disease". ... Niemann-Pick Type C (NPC) is also a lysosomal storage disorder, but instead is caused by a mutation in either NPC1 or NPC2 gene ... Cowart, Ashley (2011). Sphingolipids and Metabolic Disease. Springer. pp. 71-152. ISBN 978-1-4614-0650-1. Kornhuber, Johannes; ...
... method of detecting cholesterol in cell membranes is used clinically in the study and diagnosis of Type C Niemann-Pick disease ...
... including lysosomal storage diseases such as Niemann-Pick disease, type C and Mucolipidosis IV. When NAADP mobilizes Ca2+ from ... Acidic vesicles in some cell types may well take a leaf out of the yeasts'/plants' book and host two uptake pathways, but ... Prior to that, only high concentrations of blockers of L-type Ca2+ channels (e.g. diltiazem, dihydropyridines) could be used ( ... Both studies exploited the same novel 'clickable' NAADP photoprobe, but regardless of the different blood cell types, the ...
Reports Further Detail on Positive Data from IB1001 Multinational Clinical Trial for the Treatment of Niemann-Pick disease Type ... In 2020, IntraBio announced the successful multinational clinical trial results of the Niemann-Pick type C clinical trial. ... the company announced its plans for a multi-national pivotal trial for acetylleucine for the treatment of Niemann-Pick type C, ... which develops acetylleucine treatments for genetic and neurodegenerative diseases. Factor is Visiting Senior Fellow in ...
"Health economic evaluation of plasma oxysterol screening in the diagnosis of Niemann-Pick Type C disease among intellectually ... Besides, a recent study suggests a method of screening and diagnosing Niemann-Pick C disease by plasma oxysterol screening, ... neurodegenerative diseases, inflammatory bowel diseases, age-related macular degeneration and other pathological conditions ... Six different protein domains and structural motifs types are found in OSBP-ORPs. This is two phenylalanines in an acidic tract ...
The genetic conditions ataxia telangiectasia and Niemann Pick disease type C, as well as cerebellar essential tremor, involve ... The neurodegenerative disease spinocerebellar ataxia type 1 (SCA1) is caused by an unstable polyglutamine expansion within the ... and neurodegenerative diseases that are not known to have a genetic basis, such as the cerebellar type of multiple system ... autoimmune diseases; genetic mutations causing spinocerebellar ataxias, gluten ataxia, Unverricht-Lundborg disease, or autism; ...
Niemann-Pick type C is biochemically, genetically and clinically distinct from Niemann-Pick Types A or and B. In Types A and B ... "eMedicine - Niemann-Pick Disease : Article by Robert A Schwartz". Retrieved 2008-10-27. "Niemann-Pick Disease". Retrieved 2008- ... November 2008). "Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium". ... including Niemann-Pick Disease Type C. The US FDA has granted IntraBio a Rare Pediatric Disease Designation for N-Acetyl- ...
... a rare and fatal genetic disease, will start today, researchers announced. ... A clinical trial to evaluate a drug candidate called cyclodextrin as a possible treatment for Niemann-Pick disease type C1 (NPC ... Niemann Pick Disease Type C, Niemann-Pick Disease, Pharmaceuticals, Picks Disease, Preclinical, Research, Sickle Cell Disease ... the National Niemann Pick Disease Foundation, and Support Of Accelerated Research for Niemann -Pick Type C. ...
... a fatal neurological disease, according to results of a ... An experimental drug appears to slow the progression of Niemann ... An experimental drug appears to slow the progression of Niemann-Pick disease type C1 (NPC1), a fatal neurological disease, ... Experimental treatment for Niemann-Pick disease type C1 appears safe, effective. August 14, 2017. ScienceBlog.com ... the National Niemann-Pick Disease Foundation, and Support of Accelerated Research for NPC Disease. ...
The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid ... Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. ... Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The ... Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with ...
What is the frequency of Niemann-Pick disease?. Niemann-Pick diease type A and type B. Niemann-Pick disease types A and B is ... Niemann-Pick disease type A and type B. Niemann-Pick disease types A and B is caused by mutations in the SMPD1 gene. This gene ... Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the ... Niemann-Pick disease type C1 and type C2. Mutations in either the NPC1 or NPC2 gene cause Niemann-Pick disease type C. The ...
Metabolic diseases, Niemann Pick Disease Group, Niemann Pick Type C, Subacute-sclerosing Panencephalitis, Tay Sachs disease, ... Tags: Batten disease, Children Rare Disease Network, Gaucher Disease, Hide and Seek Foundation, MPS, Niemann Pick Type C, NORD ... The Addi and Cassi Fund - Niemann Pick Type C. Treatments & Cures for Niemann Pick Type C - Childhood Alzheimers ... lipid storage disease, Niemann Pick Type C, progressive neurodegeneration, Stem Cell Inc ...
The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. ... Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence ... Niemann-Pick disease type C Orphanet J Rare Dis. 2010 Jun 3;5:16. doi: 10.1186/1750-1172-5-16. ... Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence ...
The Addi and Cassi Fund - Niemann Pick Type C. Treatments & Cures for Niemann Pick Type C - Childhood Alzheimers ... Niemann Pick Type C, NIH, NINDS, rare disease, Schistosomiasis, sickle cell disease, Therapeutics for Rare and Neglected ... Tags: FDA, NIH, Off Label Drug Use, Rare Disease Drugs, SOAR NPC Parents group, Therapeutics for Rare and Neglected Diseases ... Ten Tips To Start Your Own Virtual BioTech To Find Treatments For Your Rare Disease. June 9, 2009 by Chris Hempel Filed under ...
Niemann-Pick type C disease, choroid plexus, extracellular vesicles, blood-CSF-barrier, autophagosomes, ALZHEIMERS-DISEASE, I ... Niemann-Pick type C (NPC) disease, sometimes called childhood Alzheimers, is a rare neurovisceral lipid storage disease with ... Niemann-Pick type C (NPC) disease, sometimes called childhood Alzheimers, is a rare neurovisceral lipid storage disease with ... Niemann-Pick type C disease,choroid plexus,extracellular vesicles,blood-CSF-barrier,autophagosomes,ALZHEIMERS-DISEASE,I ...
The role of audiology in understanding and treating Niemann-Pick disease type C ... From natural history to clinical trial: The role of audiology in understanding and treating Niemann-Pick disease type C. ... From natural history to clinical trial: The role of audiology in understanding and treating Niemann-Pick disease type C. ... From natural history to clinical trial: The role of audiology in understanding and treating Niemann-Pick disease type C ...
Metabolomic studies of lipid storage disorders, with special reference to Niemann-Pick type C disease: a critical review with ... Metabolomic studies of lipid storage disorders, with special reference to Niemann-Pick type C disease: a critical review with ... particularly Niemann-Pick type C disease. Relevant limitations of these techniques are also discussed, along with the latest ... They also show much promise for monitoring disease progression and the evaluation of therapeutic strategies and targets. ...
Pathology: Niemann-Pick disease, type B *257200 OMIM record - By selecting the cell line name, you will receive the detailed ...
... notably liver disease). Though it is well-known that NPC exacts a physical and emotional toll on both patients and caregivers, ... is a rare inherited lysosomal storage disease typified by accumulation of cholesterol and other lipids in late endosomes/ ... Niemann-Pick disease type C (NPC) is a rare progressive genetic disease caused by mutations in NPC1 or NPC2 [1, 2], which ... Niemann-Pick disease type C (NPC) is a rare inherited lysosomal storage disease typified by accumulation of cholesterol and ...
... recovery and follow-up care for Niemann-Pick disease. ... Learn about Niemann-Pick disease, find a doctor, complications ... All types of Niemann-Pick are autosomal recessive. This means that both parents are carriers. Each parent has one copy of the ... Niemann-Pick disease. NPD; Sphingomyelinase deficiency; Lipid storage disorder - Niemann-Pick disease; Lysosomal storage ... Niemann-Pick disease (NPD) is a group of diseases passed down through families (inherited) in which fatty substances called ...
ICD-10 code E75.24 for Niemann-Pick disease is a medical classification as listed by WHO under the range -Metabolic disorders . ... Niemann-Pick disease type D. E75.244. Niemann-Pick disease type A/B ... ICD-10-CM Code for Niemann-Pick disease E75.24 ICD-10 code E75.24 for Niemann-Pick disease is a medical classification as ... listed by WHO under the range - Endocrine, nutritional and metabolic diseases .. Subscribe to Codify by AAPC and get the code ...
2008) Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14: ... 2003) Niemann-Pick disease type C. Clin Genet 64:269-281, doi:10.1034/j.1399-0004.2003.00147.x, pmid:12974729. ... 2005) Niemann-Pick type C disease and intracellular cholesterol trafficking. J Biol Chem 280:20917-20920, doi:10.1074/jbc. ... 2007) The adult form of Niemann-Pick disease type C. Brain 130:120-133, doi:10.1093/brain/awl260, pmid:17003072. ...
The lysosomal storage diseases Niemann-Pick disease type C (NPC) is caused by mutations predominantly in the lysosomal integral ... Niemann-Pick disease type C is a rare, devastating, inherited lysosomal storage disease with a unique cellular phenotype ... In this review we highlight the impact of the disease on innate immune activities in both the central nervous system (CNS) and ... In particular pro-inflammatory responses promote disease progression and anti-inflammatory drugs provide benefit in animal ...
Learn and reinforce your understanding of Niemann-Pick disease types A and B (NORD). ... Niemann-Pick disease types A and B (NORD) Videos, Flashcards, High Yield Notes, & Practice Questions. ...
Niemann-Pick Disease Type C Associated with Fuchs Heterochromic Iridocyclitis In this study, we report a 26-year-old female ... case of Niemann-Pick disease type C in association with Fuchs heterochromic iridocyclitis who was admitted with the complaint ... Localization of the murine Niemann-Pick C1 protein to two distinct intracellular compartments by: William S. Garver, et al. ...
Niemann-Pick Disease Type C2 (NPC2): Read more about Symptoms, Diagnosis, Treatment, Complications, Causes and Prognosis. ... supranuclear ophthalmoplegia, Niemann-Pick disease type D, Niemann-Pick disease Nova Scotian type Niemann-Pick disease (NPD) is ... What is the prognosis for an individual with Niemann-Pick Disease Type C2? Niemann-Pick disease type C shows variable disease ... Nieman-pick types Niemann-Pick disease type A (neurological type) The symptoms include: hepatosplenomegaly (an enlarged liver ...
In the terminal disease stage, loss of APP caused pleiotropic differential expression of the vast majority of cytokines ... In that regard, neuroinflammation occurs early in the disease and we have recently unveiled an atypical pattern of interferon ... Niemann-Pick disease type C (NPC) is a progressive neurodegenerative condition that results in early fatality. NPC is inherited ... APP is a disease modifier of Niemann-Pick disease type C (NPC). The loss of the App gene in the NPC mouse model BALB/cNctr-Npc1 ...
It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human ... is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell- ... Niemann-Pick type C (NPC) disease is a rare progressive lysosomal storage disorder caused by mutations in either the NPC1 or ... Andrade, G.N., Molholm, S., Butler, J.S. et al. Atypical multisensory integration in Niemann-Pick type C disease - towards ...
Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron ... suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease. ... Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of ... Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the ...
Niemann-Pick disease type C (NPC) is a recessive genetic lysosomal storage disease caused by mutations in the NPC1 or NPC2 ... A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human ... A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human ... Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention ...
Niemann-Pick disease *Niemann-Pick disease type A (NPA). *Niemann-Pick disease type B (NPB) ... Niemann-Pick disease type C (NPD-C) *pronounced CNS involvement with atrophy or white matter T2 signal increase on MRI 1 ... Niemann-Pick disease type A (NPD-A) *severe hepatosplenomegaly in infancy. *severe central nervous system involvement, with ... Niemann-pick disease type a presenting as unilateral tremors. (2016) Indian Pediatrics. 49 (11): 919. doi:10.1007/s13312-012- ...
... how niemann-pick type c disease affects the brain, Niemann-Pick Disease, Niemann-Pick Type C Disease, Parker Stults, The ... Trial National Institutes of Health Niemann-Pick Niemann-Pick Childrens Fund Niemann-Pick Type C Niemann-Pick Type C Disease ... Tags: Niemann-Pick Childrens Fund, Niemann-Pick Type C Disease, Presentation , 2 Comments » ... More importantly I hope we can generate awareness for Niemann-Pick Type C disease and rare disease in general. You can also ...
Correction of Niemann-Pick type C1 disease with the histone deacetylase inhibitor valproic acid. Kanagaraj Subramanian, Darren ... Old Dogs Can Learn New Tricks: using existing therapeutic compounds to treat Niemann-Pick type C disease ... An example of an LSD is Nieman-Pick type C (NPC) disease, which has a broad phenotype that includes enlargement of the spleen, ... This domain is where the most prevalent disease-causing mutations are found, including I1061T. The hypothesis is that these ...
Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron ... suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease. ... Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of ... Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the ...
Gene Therapy for Niemann-Pick Disease Type C * E-100-2017-0 TAB-3414 Codon-Optimized Gene Therapy for Niemann-Pick Disease Type ... Niemann-Pick Disease, type C (NPC) is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients ... Assay for Predicting the Time of Onset of Niemann-Pick Disease Type C (NPC) ... Assay for Predicting the Time of Onset of Niemann-Pick Disease Type C (NPC) ...
  • Niemann-Pick type C (NPC) (colloquially, "Childhood Alzheimer's") is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. (wikipedia.org)
  • 5% are caused by mutations in the NPC2 gene, referred to as type C2. (wikipedia.org)
  • Mutations in either the NPC1 or NPC2 gene cause Niemann-Pick disease type C. The proteins produced from these genes are involved in the movement of lipids within cells. (hdkino.org)
  • The disease is caused by loss-of-function mutations in the Npc1 or Npc2 gene which both result into lipid accumulation in the late endosomes and lysosomes. (ugent.be)
  • Niemann-Pick disease type C (NPC) is a neurodegenerative disease inherited in an autosomal recessive pattern [ 1 ], with mutations in the NPC1 gene accounting for approximately 95% of all reported cases and the remaining 5% of the cases resulting from mutations in the NPC2 gene. (biomedcentral.com)
  • Functionally, the biological roles of NPC1and NPC2 are not well defined, a shortcoming that has hampered our understanding of the mechanistic etiology of the disease. (biomedcentral.com)
  • Niemann-Pick type C (NPC) disease is a rare progressive lysosomal storage disorder caused by mutations in either the NPC1 or NPC2 gene, with about 95% of cases attributable to the former [ 1 ],[ 2 ]. (biomedcentral.com)
  • Niemann-Pick disease type C is not caused by a deficiency of sphlingomyelinase but by a lack of the NPC1 or NPC2 proteins. (nih.gov)
  • This process depends on the endo-lysosomal sterol transfer protein Niemann Pick C2 (NPC2). (nature.com)
  • NPC disease is caused by dysfunction of either the NPC1 or NPC2 protein. (nature.com)
  • Lysosomal storage disorders (LSDs) are predominantly very rare recessive autosomal neurodegenerative diseases.Sphingolipidoses, a sub-group of LSDs, result from defects in lysosomal enzymes involved in sphingolipid catabolism, and feature disrupted storage systems which trigger complex pathogenic cascades with other organelles collaterally affected. (ntu.ac.uk)
  • Autosomal recessive is one of several ways that a trait, disorder, or disease can be passed down through families. (mountsinai.org)
  • An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop. (mountsinai.org)
  • Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. (biomedcentral.com)
  • Niemann-P ick disease (NPD) is actually a collection of a number of distinct autosomal recessive lysosomal storage diseases . (radiopaedia.org)
  • NPD types A and B are inherited as autosomal recessive traits. (medscape.com)
  • Niemann-Pick disease is a group of autosomal recessive disorders caused by an accumulation of fat and cholesterol in cells of the liver, spleen, bone marrow, lungs, and, in some instances, brain. (nih.gov)
  • Niemann-Pick type C (NPC) disease is an autosomal recessive disease of lysosomal lipid storage disorder caused by mutations in either th. (nel.edu)
  • Enlargement of the spleen or liver frequently becomes less apparent with time, in contrast to the progression of other lysosomal storage diseases such as Niemann-Pick disease, Types A and B or Gaucher disease. (wikipedia.org)
  • Gaucher disease is caused by a deficiency of the enzyme glucocerebrosidase. (nih.gov)
  • Type 2 (acute infantile neuropathic Gaucher disease) typically begins within three months of birth. (nih.gov)
  • It is characterized by slowly progressive yet milder neurologic symptoms compared to type 2 Gaucher disease. (nih.gov)
  • Because Niemann-Pick disease type B resembles type 1 Gaucher disease to a considerable degree, one might anticipate that enzyme replacement and, ultimately, gene therapy will eventually be helpful in patients with Niemann-Pick disease type B. (medscape.com)
  • Misdiagnosis of Niemann-Pick disease type C as Gaucher disease. (medscape.com)
  • The clinical manifestations of types Niemann-Pick types C1 and C2 are similar because the respective genes are both involved in egress of lipids, particularly cholesterol, from late endosomes or lysosomes. (wikipedia.org)
  • NPC patients who participated in the interviews possessed a range of disease severity, central manifestations, and variable baseline characteristics such as age of symptom onset, age of diagnosis, current treatment, and geographical location. (biomedcentral.com)
  • Prospective, Randomized, Double-Blind, Sham-Controlled Trial of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in Subjects with Neurologic Manifestations of Niemann-Pick Type C1 (NPC1) Disease. (bepress.com)
  • Niemann-Pick disease types A and B is caused by mutations in the SMPD1 gene. (hdkino.org)
  • As NPC patients, who carry NPC1 mutations, have shown to share several pathological features with Alzheimer's disease (AD) and we and others have previously shown that AD is associated with a dysfunctionality of the blood-cerebrospinal fluid (CSF) barrier located at choroid plexus, we investigated the functionality of this latter barrier in NPC1 pathology. (ugent.be)
  • The lysosomal storage diseases Niemann-Pick disease type C (NPC) is caused by mutations predominantly in the lysosomal integral membrane protein NPC1 and clinically presents as a progressive neurodegenerative disorder. (ox.ac.uk)
  • Most mutations in individuals with NPC are unique to the pedigree, are not localized to specific domains and have not been correlated to time of onset or disease severity. (nih.gov)
  • It belongs to a family know as lysosomal storage diseases and is caused by mutations leading to defective NPC protein. (npuk.org)
  • In Nova Scotia, a population of affected French-Acadians were previously designated as having Niemann-Pick disease type D, however, it was shown that these individuals have mutations in the gene associated with Niemann-Pick disease type C1. (medlineplus.gov)
  • Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C. J Neurol Neurosurg Psychiatry . (medscape.com)
  • Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations. (lu.se)
  • Mutations in the NPC1 are associated with type C NIEMANN-PICK DISEASE. (bvsalud.org)
  • Niemann-Pick type C (NPC) disease, sometimes called childhood Alzheimer's, is a rare neurovisceral lipid storage disease with progressive neurodegeneration leading to premature death. (ugent.be)
  • Intriguingly, brains of adult NPC patients exhibit neurofibrillary tangles, a characteristic hallmark of Alzheimer's disease (AD). (ulaval.ca)
  • research that may also help millions of people suffering from HIV/Aids, Ebola, heart disease, stroke, Alzheimer's disease and other disorders that appear to be related to cholesterol. (danasangels.org)
  • Niemann-Pick disease is classified into types based upon symptoms and genetic causes. (hdkino.org)
  • Symptoms of Niemann-Pick disease are related to the type of fatty products that accumulate, which organs are affected, and to what degree. (hdkino.org)
  • Niemann-Pick disease type C (NPC) is a rare inherited lysosomal storage disease typified by accumulation of cholesterol and other lipids in late endosomes/lysosomes, thereby resulting in a spectrum of neurological, psychiatric, and systemic symptoms (notably liver disease). (biomedcentral.com)
  • The early stages of the disease may only cause a few symptoms. (mountsinai.org)
  • Type B symptoms are usually milder. (mountsinai.org)
  • Type A Niemann-Pick disease usually presents symptoms within months of birth. (symptoma.com)
  • We have shown that lysosomal staining in patient derived fibroblasts quantified by FACS analysis is directly correlated to the time of onset of disease symptoms. (nih.gov)
  • Chest radiography in NPD type B reveals a typical reticulonodular pattern of infiltration, even in patients with no overt pulmonary symptoms. (medscape.com)
  • These types are classified on the basis of genetic cause and the signs and symptoms of the condition. (medlineplus.gov)
  • The signs and symptoms of this type are similar to type A, but not as severe. (medlineplus.gov)
  • Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. (medlineplus.gov)
  • Symptoms vary by type but may include intellectual disability and neurologic problems. (msdmanuals.com)
  • Children with type C develop symptoms during childhood, with seizures and neurologic deterioration. (msdmanuals.com)
  • Approximately 15% of patients follow a primary progressive or progressive relapsing course from disease onset, usually characterized by symptoms of progressive myelopathy (gait instability, spasticity, bladder symptoms) and cognitive impairment. (medscape.com)
  • The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). (nih.gov)
  • 2, 13, 15, 24 Hepatosplenomegaly is the most important clinical finding in NPD type B, 11, 25 with splenomegaly being more marked than hepatomegaly. (symptoma.com)
  • It is commonly known as Niemann-Pick disease (NPD) type A, type B, or type A/B. The original description of NPD referred to what is currently termed NPD type A, which is a fatal disorder of early childhood characterized by failure to thrive , hepatosplenomegaly, and a rapidly progressive neurodegenerative course that leads to death by age 2-3 years. (medscape.com)
  • Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). (medlineplus.gov)
  • In this review we highlight the impact of the disease on innate immune activities in both the central nervous system (CNS) and peripheral tissues and discuss their contributions to pathology and the underlying mechanisms. (ox.ac.uk)
  • As a consequence, lipids that are normally cleared by the lysosome build-up in tissues and organs, including the brain, and drive the disease pathology. (npuk.org)
  • A new surrogate marker for CNS pathology in Niemann-Pick disease type C? (medscape.com)
  • Niemann-Pick type C is biochemically, genetically and clinically distinct from Niemann-Pick Types A or and B. In Types A and B, there is complete or partial deficiency of the lysosomal enzyme called acid sphingomyelinase. (wikipedia.org)
  • In Niemann-Pick type C, large amounts of free or unesterified cholesterol accumulate in lysosomes, and leads to relative deficiency of this molecule in multiple membranes and for steroid synthesis. (wikipedia.org)
  • Niemann-Pick types A and B result from accumulation of the fatty substance called sphingomyelin, due to deficiency of an enzyme called sphingomyelinase. (nih.gov)
  • In types A and B, the deficiency of a specific enzyme called sphingomyelinase results in the accumulation of sphingomyelin (a product of fat metabolism). (msdmanuals.com)
  • Niemann-Pick Disease Type C (NPC) Pipeline Insight, 2023 " report by DelveInsight outlines a comprehensive assessment of the present clinical/non-clinical development activities and growth prospects across the Niemann-Pick Disease Type C Market. (thesunshinereporter.com)
  • An experimental drug appears to slow the progression of Niemann-Pick disease type C1 (NPC1), a fatal neurological disease, according to results of a clinical study led by researchers at the National Institutes of Health. (scienceblog.com)
  • Compared to untreated patients we followed in an earlier study, participants who received VTS-270 scored better on a scale used to evaluate disease severity and progression, including elements such as speech, cognition and mobility. (scienceblog.com)
  • Their progress was compared to a previous group of 21 NPC1 participants enrolled in an earlier study that documented disease progression. (scienceblog.com)
  • The authors believe these differences indicate that treatment with the drug can stabilize or slow disease progression. (scienceblog.com)
  • They also show much promise for monitoring disease progression and the evaluation of therapeutic strategies and targets. (ntu.ac.uk)
  • In particular pro-inflammatory responses promote disease progression and anti-inflammatory drugs provide benefit in animal models of the disease and are an attractive target for clinical intervention in this disorder. (ox.ac.uk)
  • Targeting inflammation in the brain therefore represents a potential clinical intervention strategy that aims to slow the rate of disease progression and improve quality of life. (ox.ac.uk)
  • In vivo studies have identified N-acetyl-L-leucine to be the active isomer of N-acetyl-DL-leucine and can restore neuronal function and protect against/delay disease progression in multiple neurological circuits of the brain. (inpda.org)
  • It has later symptom onset compared with type A and slower neurologic and visceral disease progression compared with type A and type B. (medscape.com)
  • With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident. (medscape.com)
  • In patients with Niemann-Pick disease type C, cholesterol-lowering agents have some effect on the hepatic storage of lipid but not on the progression of central nervous system disease. (medscape.com)
  • The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. (nih.gov)
  • This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease. (nih.gov)
  • the diagnosis of Niemann-Pick disease type C was based on finding foamy storage cells in bone marrow aspirates. (wiley.com)
  • Application of N-palmitoyl-O-phosphocholineserine for diagnosis and assessment of response to treatment in Niemann-Pick type C disease. (rush.edu)
  • At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement. (medscape.com)
  • The diagnosis is based on the results of prenatal screening tests, newborn screening tests (for types A and B), or biopsy of the liver. (msdmanuals.com)
  • Cataplexy leading to the diagnosis of Niemann-Pick disease type C. Pediatr Neurol . (medscape.com)
  • Vanier MT, Boue J, Dumez Y. Niemann-Pick disease type B: first-trimester prenatal diagnosis on chorionic villi and biochemical study of a foetus at 12 weeks of development. (medscape.com)
  • Wenger DA, Kudoh T, Sattler M, Palmieri M, Yudkoff M. Niemann-Pick disease type B: prenatal diagnosis and enzymatic and chemical studies on fetal brain and liver. (medscape.com)
  • Lysosomal storage diseases are inherited monogenic disorders in which lysosome function is compromised. (ox.ac.uk)
  • Lipid storage diseases (also known as lipidoses) are a group of inherited metabolic disorders in which harmful amounts of fatty materials (lipids) accumulate in various cells and tissues in the body. (nih.gov)
  • Disorders in which intracellular material that cannot be metabolized is stored in lysosomes are called lysosomal storage diseases. (nih.gov)
  • When cellular cholesterol trafficking is interrupted, it can lead to fatal disorders, such as the neurodegenerative Niemann Pick type C (NPC) disease, in which cholesterol accumulates in late endosomes and lysosomes (LE/LYSs) and fails to reach the homeostatic sensing machinery in the ER 4 . (nature.com)
  • Azafaros is developing the compound as a potentially disease-modifying treatment in severe metabolic disorders including GM1 and GM2 gangliosidoses and NP-C. Enrollment of the first patient in the study is an important milestone for Azafaros in its mission to bring new treatment options to these patients and their families. (dutchnews.nl)
  • AZ-3102 is an orally available azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement, including GM1 and GM2 gangliosidoses and Niemann-Pick disease type C (NP-C). (dutchnews.nl)
  • GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are lysosomal storage disorders caused by the accumulation of GM1 or GM2 gangliosides, respectively, in the central nervous system (CNS), resulting in progressive and severe neurological impairment and early death. (dutchnews.nl)
  • This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. (medscape.com)
  • In Niemann-Pick type C, the protein product of the major mutated gene NPC1 is not an enzyme but appears to function as a transporter in the endosomal-lysosomal system, which moves large water-insoluble molecules through the cell. (wikipedia.org)
  • Localization of the murine Niemann-Pick C1 protein to two distinct intracellular compartments by: William S. Garver, et al. (uitm.edu.my)
  • Genes Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body or the code for functional ribonucleic. (msdmanuals.com)
  • Niemann-Pick disease type C is a rare, devastating, inherited lysosomal storage disease with a unique cellular phenotype characterized by lysosomal accumulation of sphingosine, various glycosphingolipids and cholesterol and a reduction in lysosomal calcium. (ox.ac.uk)
  • Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120,000 live births. (nih.gov)
  • Niemann-Pick type C1 (NPC1) disease is a rare neurovisceral disorder characterized by intracellular accumulation of unesterified cholesterol, sphingolipids, and other lipids in the lysosomal compartment. (jneurosci.org)
  • Niemann-Pick disease Type C (NPC) is a genetic, progressively debilitating, and often fatal neurovisceral disease. (npuk.org)
  • NPD type A/B is an overlapping disease entity that is also known as chronic neurovisceral ASMD or NPD B variant. (medscape.com)
  • In 2009, the NIH Therapeutics for Rare and Neglected Diseases (TRND) program, which is now led by NCATS, selected NPC cyclodextrin as one of its initial pilot projects to repurpose cyclodextrin from its conventional use as an ingredient in other drugs to a therapeutic for this rare disorder. (news-medical.net)
  • The multidisciplinary nature of this collaboration establishes a generalizable model that can be used in the pursuit of treatment candidates for rare and neglected diseases,' said John McKew, Ph.D., acting director of the NCATS Division of Pre-Clinical Innovation, chief of the Therapeutic Development Branch and director of TRND. (news-medical.net)
  • Finally, CGS21680 reduces cholesterol accumulation (Filipin III staining), which is the main criterion currently used for identification of a compound or pathway that would be beneficial for NPC disease, and such an effect is prevented by the Ca 2+ chelator BAPTA-AM. Our findings strongly support the hypothesis that A 2A R agonists may represent a therapeutic option for NPC1 and provide insights on their mechanisms of action. (jneurosci.org)
  • Therapeutic trials for Niemann-Pick disease (NPD) have had only limited effectiveness. (medscape.com)
  • The Molecular and Genetic Basis of Neurologic and Psychiatric Disease. (radiopaedia.org)
  • This disease causes many neurologic problems. (msdmanuals.com)
  • Children with type A (the most severe form) fail to grow normally and have several neurologic problems. (msdmanuals.com)
  • Dr. Porter also is conducting a natural history study of NPC to collect health information from patients to understand how the disease develops. (news-medical.net)
  • As part of its mission, the NIDCD Audiology Unit provides hearing tests to patients with rare diseases such as NPC being treated at the National Institutes of Health's Clinical Center. (nih.gov)
  • Key to advancing new treatments for this and related lysosomal diseases with neural involvement is the development of objective biomarkers of neurological function against which the efficacy of new drugs can be tested in human patients. (biomedcentral.com)
  • Copenhagen, July 21, 2019 - Orphazyme A/S (ticker: ORPHA.CO), a biopharmaceutical company dedicated to developing treatments for patients living with rare diseases, today announces that it has had a positive meeting with the FDA and remains on track to submit an NDA for arimoclomol for NPC in H1 2020. (npuk.org)
  • Orphazyme is a biopharmaceutical company focused on bringing novel treatments to patients living with life-threatening or debilitating rare diseases. (npuk.org)
  • The National Niemann-Pick Disease Foundation's Executive Director Joslyn Crowe commented: "The exciting results of the IB1001 clinical trial bring new levels of hope and optimism to patients and families affected by Niemann-Pick disease type C. There continues to be a critical need for new therapies to treat NPC and we are so grateful to our partners like IntraBio for their continued commitment to finding new treatments like IB1001. (inpda.org)
  • IB1001-201 (NCT03759639) is a multinational clinical trial evaluating IB1001 for both the symptomatic and neuroprotective, disease-modifying treatment for adult and pediatric patients with NPC. (inpda.org)
  • For example, in familial hypercholesterolemia, enzymes do not receive the signals that typically inhibit cholesterol synthesis, so that excessive production of cholesterol occurs, leading to early coronary vascular disease and strokes in patients. (newworldencyclopedia.org)
  • Pancytopenia may be present secondary to the enlarged spleen in patients with NPD, and reduced high-density-lipoprotein cholesterol (HDL-C) fraction is common in NPD type B. (medscape.com)
  • Adult patients with elevated serum cholesterol due to NPD type B should be treated to bring serum cholesterol concentration into the normal range. (medscape.com)
  • Transfusion of blood products may be necessary for acute episodes of bleeding secondary to hypersplenism and thrombocytopenia in NPD type B patients. (medscape.com)
  • The clinical trial is being conducted in Brazil and the US and will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics across two doses of its lead asset, AZ-3102, in patients with GM2 gangliosidosis and Niemann-Pick disease type C (NP-C). (dutchnews.nl)
  • For Niemann-Pick disease type A patients, currently, no effective treatment exists. (medscape.com)
  • Bone marrow transplantation has been attempted in a few patients with Niemann-Pick disease type B, and encouraging results are reported. (medscape.com)
  • Patients with Niemann-Pick disease type C or D are commonly prescribed a low-cholesterol dietary regimen. (medscape.com)
  • NPC1 defect results in abnormal platelet formation and function: studies in Niemann-Pick disease type C1 patients and zebrafish. (bvsalud.org)
  • A clinical trial to evaluate a drug candidate called cyclodextrin as a possible treatment for Niemann-Pick disease type C1 (NPC), a rare and fatal genetic disease, will start today, researchers announced. (news-medical.net)
  • The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. (nih.gov)
  • The valuable advice we have received from health authorities in both the US and Europe increases our optimism that we may soon be able to provide an important treatment option for NPC, a severely debilitating and fatal disease that predominantly affects children. (npuk.org)
  • 2-Hydroxy-propyl-beta-cyclodextrin (HP beta CD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. (ncl.ac.uk)
  • Dana's Angels Research Trust is a non-profit organization that funds research into a rare disease, Niemann-Pick type C (NPC), a fatal, cholesterol-storage disease affecting children. (danasangels.org)
  • Type C is always fatal, and most children die before age 20. (msdmanuals.com)
  • The researchers also evaluated the drug's effectiveness using a neurological severity score, where higher scores indicate more severe effects from the disease. (scienceblog.com)
  • As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. (cdc.gov)
  • The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. (cdc.gov)
  • Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. (nih.gov)
  • Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of multiple lipids in the late endosome/lysosomal system and reduced acidic store calcium. (ox.ac.uk)
  • Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal disorder characterized by sphingolipid and cholesterol storage in the late endocytic system. (ox.ac.uk)
  • Niemann-Pick Type C (NPC) is a rare genetic disorder characterized by progressive cell death in various tissues, particularly in the cerebellar Purkinje cells, with no known cure. (ox.ac.uk)
  • Niemann-Pick disease type C (NPC) is a rare lysosomal storage disorder causing an intracellular lipid trafficking defect and varying damage to the spleen, liver, and central nervous system. (ulaval.ca)
  • A metabolic disorder is any disease or disorder that negatively affects the biochemical reactions through which individual animal cells process nutrient molecules (such as the components of carbohydrates , proteins , and fats ) to yield energy or perform the functions necessary to sustain life (such as building complex molecules and creating cellular structure). (newworldencyclopedia.org)
  • 166 damaging and 21 benign amino acid substitutions in neurodegenerative disorder Niemann-Pick disease type C (NP-C). (lu.se)
  • Thank you Dr. Francis Collins, Dr. Chris Austin, Dr. John McKew and others at the NIH who are all involved in driving the National Institutes of Health's Therapeutics for Rare and Neglected Diseases (TRND) program forward. (addiandcassi.com)
  • As per DelveInsight's assessment, globally, about 13+ key pharma and biotech companies are working on 13+ pipeline drugs in the Niemann-Pick Disease Type C therapeutics landscape based on different Routes of Administration (ROA), Mechanism of Action (MOA), and molecule types. (thesunshinereporter.com)
  • It outlines the major Niemann-Pick Disease Type C companies involved in targeted therapeutics development with respective active and inactive (dormant or discontinued) projects. (thesunshinereporter.com)
  • 13+ key companies are developing therapies for Niemann-Pick Disease Type C. Currently, Orphazyme is leading the therapeutics market with its Niemann-Pick Disease Type C drug candidates in the most advanced stage of clinical development. (thesunshinereporter.com)
  • In 2022, the compound received Fast Track Designation for GM1 and GM2 gangliosidoses as well as NP-C and Orphan Drug Designations (ODD) for GM2 gangliosidosis (Sandhoff and Tay-Sachs Diseases) and NP-C from the FDA. (dutchnews.nl)
  • Computed tomography (CT) scanning or magnetic resonance imaging (MRI) in NPD type B can be used to quantify liver and spleen volumes. (medscape.com)
  • Acid sphingomyelinase is responsible for the conversion of a fat ( lipid ) called sphingomyelin into another type of lipid called ceramide. (hdkino.org)
  • NPD types A and B occur when cells in the body do not have an enzyme called acid sphingomyelinase (ASM). (mountsinai.org)
  • 152 disease (XLA)-associated single amino acid-substitution caused amino acid substitions (SNAVs) in 91 residues. (lu.se)
  • Over time, cell loss impairs function of tissues and organs including the brain, lungs , spleen, and liver in people with Niemann-Pick disease types A and B. (hdkino.org)
  • Niemann-Pick disease (NPD) is a group of diseases passed down through families (inherited) in which fatty substances called lipids collect in the cells of the spleen, liver, and brain. (mountsinai.org)
  • Type C1 is a variant of type C. It involves a defect that interferes with how cholesterol moves between brain cells. (mountsinai.org)
  • E.R. physician Dr. Travis Stork explains how Niemann-Pick Type C disease affects the brain. (bripardun.com)
  • In common with other neurodegenerative diseases, activation of the innate immune system occurs in the brain resulting in neuro-inflammation. (ox.ac.uk)
  • Longitudinal MEMRI analysis of brain phenotypes in a mouse model of Niemann-Pick Type C disease. (ox.ac.uk)
  • Previous imaging studies revealed significant brain volume differences between mutant and wild-type animals, but stopped short of making volumetric comparisons of the cerebellar sub-regions. (ox.ac.uk)
  • In this study, we present longitudinal manganese-enhanced MRI (MEMRI) data from cohorts of wild-type, heterozygote carrier, and homozygote mutant NPC mice, as well as deformation-based morphometry (DBM) driven brain volume comparisons across genotypes, including the cerebellar cortex, white matter, and nuclei. (ox.ac.uk)
  • MRI of the brain in NPD type A may be normal or may show signs of white matter involvement. (medscape.com)
  • Type B (juvenile onset) does not generally affect the brain but most children develop ataxia, damage to nerves exiting from the spinal cord (peripheral neuropathy), and pulmonary difficulties that progress with age. (nih.gov)
  • Furthermore, drugs elevating Ca 2+ levels correct the NPC1 phenotype in vitro , reduce neurological disturbances, and prolong survival in a mouse model of NPC1 disease. (jneurosci.org)
  • At the cellular level, the disease phenotype is broad, affecting multiple functions, such as endosomal lipid accumulation, calcium dysregulation, neuroinflammation, mitochondrial dysfunction, amyloid peptide Aβ accumulation and tau hyperphosphorylation and aggregation. (biomedcentral.com)
  • An example of an LSD is Nieman-Pick type C (NPC) disease, which has a broad phenotype that includes enlargement of the spleen, ataxia, and psychiatric problems, such as dementia. (biologists.com)
  • citation needed] In the terminal stages of Niemann-Pick type C disease, the patient is bedridden, with complete ophthalmoplegia, loss of volitional movement and severe dementia. (wikipedia.org)
  • infants thus identified typically have severe neonatal liver disease with jaundice and persistent ascites . (symptoma.com)
  • Some severe diseases, such as many of the lipid storage diseases, currently have no effective therapy. (newworldencyclopedia.org)
  • Type A, the most severe form, begins in early infancy. (nih.gov)
  • People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. (medlineplus.gov)
  • All other ebolaviruses found in Africa can cause severe human disease (only 1 nonfatal infection with Taï Forest virus has been reported) ( 9 ). (cdc.gov)
  • Conclusions: These data suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease. (ox.ac.uk)
  • Niemann-Pick type C affects an estimated 1:150,000 people. (wikipedia.org)
  • Although each Rare Disease affects a small number of people, taken all together rare diseases affect millions of people in the world. (addiandcassi.com)
  • NIDCD intramural scientists were the first to detail the affects of NPC on hearing, and are now members of a team, led by the National Institute of Child Health and Human Development (NICHD), working on a clinical trial to test a promising new therapy for the disease. (nih.gov)
  • Types C and C1 usually affects school-age children. (mountsinai.org)
  • While NPC affects all cell types in the body, the main disease feature is the progressive neurodegeneration that results in premature death [ 1 ]. (biomedcentral.com)
  • Due to Niemann-Pick Type C disease, the affects of it all as you can see are weighing in as they struggle to hold and complete the normal functions of eating that so many of us by default take for granted. (bripardun.com)
  • The disease affects males and females equally. (nih.gov)
  • Niemann-Pick disease is a condition that affects many body systems. (medlineplus.gov)
  • TRND researchers work with project collaborators to conduct preclinical studies advancing potential treatments for rare and neglected diseases to human clinical trials. (news-medical.net)
  • IB1001 is part of IntraBio's broad platform of novel treatments to provide neuroprotection, disease modification, and symptomatic relief from multiple neurodegenerative and lysosomal storage diseases," noted Mallory Factor, Chairman of IntraBio Inc. "We are currently trialing IB1001 treatment of GM2 (Tay-Sachs and Sandhoff disease) and Ataxia-Telangiectasia (AT). (inpda.org)
  • The Niemann-Pick Disease Type C Pipeline report embraces in-depth commercial, regulatory, and Niemann-Pick Disease Type C clinical trial assessment of the pipeline products from the pre-clinical developmental phase to the marketed phase. (thesunshinereporter.com)
  • Some children with Niemann-Pick disease do not survive early childhood, while those with certain forms (type B, type C1, type C2) can survive into adulthood. (hdkino.org)
  • Time of onset of the disease varies from neonatal periods to adulthood. (nih.gov)
  • NPD type B (chronic visceral ASMD) is a milder, non-neuronopathic form with later onset and longer survival, sometimes into adulthood. (medscape.com)
  • Type 3 (chronic neuronopathic form) can begin at any time in childhood or even in adulthood. (nih.gov)
  • People with Niemann-Pick disease type B usually survive into adulthood. (medlineplus.gov)
  • People with these types may survive into adulthood. (medlineplus.gov)
  • In that regard, neuroinflammation occurs early in the disease and we have recently unveiled an atypical pattern of interferon signaling in pre-symptomatic Npc1 −/− mice, with microglial activation, anti-viral response, activation of antigen-presenting cells, and activation and chemotaxis of T lymphocytes as the key affected pathologic pathways. (biomedcentral.com)
  • citation needed] Progressive neurological disease is the hallmark of Niemann-Pick type C disease, and is responsible for disability and premature death in all cases beyond early childhood. (wikipedia.org)
  • Children with Niemann-Pick disease type A generally do not survive past early childhood. (medlineplus.gov)
  • Durusu Tanriover M, Demir Onal E, Uslu N, Onder S, Gurakan F. Chronic liver disease or tuberculosis: could it be Niemann-Pick disease? (medscape.com)
  • Multiple sclerosis is a common, chronic demyelinating neurological disease primarily affecting young adults, with a prevalence of ~0.1% in the Caucasian population (Miller and Leary, 2007). (medscape.com)
  • Cognition and anatomy of adult Niemann-Pick disease type C: Insights for the Alzheimer field. (ulaval.ca)
  • Type C may appear early in life or develop in the teen or even adult years. (nih.gov)
  • Subclinical course of adult visceral Niemann-Pick type C1 disease. (medscape.com)
  • Type D Niemann-Pick has only been found in the French Canadian population of Yarmouth County, Nova Scotia, and is now known to be allelic with Niemann-Pick type C. Genealogical research indicates that Joseph Muise (c. 1679-1729) and Marie Amirault (1684 - c. 1735) are common ancestors to all people with Type D. This couple is the most likely origin for the type D variant. (wikipedia.org)
  • One valuable approach to gaining insights into the global impact of lysosomal dysfunction is through metabolomics, which represents a discovery tool for investigating disease-induced modifications in the patterns of large numbers of simultaneously-analysed metabolites, which also features the identification of biomarkers Here, the scope and applications of metabolomics strategies to the investigation of sphingolipidoses is explored in order to facilitate our understanding of the biomolecular basis of these conditions. (ntu.ac.uk)
  • This review therefore surveys the benefits of applying 'state-of-the-art' metabolomics strategies, both univariate and multivariate, to sphingolipidoses, particularly Niemann-Pick type C disease. (ntu.ac.uk)
  • Types A and B are sphingolipidoses and are caused by a buildup of sphingomyelin in the tissues. (msdmanuals.com)
  • However, the participants, most of whom had already experienced hearing loss because of the disease, had additional hearing loss after treatment. (scienceblog.com)
  • There is no treatment for Niemann-Pick disease. (hdkino.org)
  • Since the disease presents with a broad heterogenous clinical spectrum, the involved disease mechanisms are still incompletely understood and this hampers finding an effective treatment. (ugent.be)
  • Disease Designation (USA), and Fast Track designation (USA) for the treatment of NPC. (npuk.org)
  • The statistically significant and clinically meaningful response in primary and topline secondary endpoints with IB1001, together with its compelling safety profile, easy oral administration [sachet mixed with water] affirm the very favorable risk/benefit profile of IB1001 as a treatment for this devastating disease. (inpda.org)
  • The report provides detailed insights into the emerging therapies for Niemann-Pick Disease Type C treatment and the aggregate therapies developed by major pharma companies. (thesunshinereporter.com)
  • The first disease-specific enzyme replacement treatment for non-central nervous system (non-CNS) ASMD, olipudase alfa, was approved by the US Food and Drug Administration (FDA) in August 2022. (medscape.com)
  • BOMV binds to the same Niemann-Pick C1 endosomal receptor for cell entry as other ebolaviruses ( 5 ), and recent serologic evidence of a cleared human BOMV infection has been reported ( 10 ). (cdc.gov)
  • The pathologic hallmark in NPD types A and B is the histochemically characteristic lipid-laden foam cell, often termed the Niemann-Pick cell, on bone marrow examination. (medscape.com)
  • What is the Niemann-Pick disease inheritance pattern? (hdkino.org)
  • Indeed, it has been demonstrated that HDAC inhibitors (HDACi) can impact cholesterol homeostasis in NPC1 disease models. (biologists.com)
  • Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. (medscape.com)
  • Type C occurs when the body cannot properly break down cholesterol and other fats (lipids). (mountsinai.org)
  • Niemann-Pick disease type C occurs when the body is not able to break down cholesterol and other lipids. (msdmanuals.com)
  • Niemann- Pick disease is a genetic disease that leads to the accumulation of fatty products in cells, eventually causing their death. (hdkino.org)
  • The accumulation of lipids as well as the cell dysfunction eventually leads to cell death, causing the tissue and organ damage seen in Niemann-Pick disease types C1 and C2. (hdkino.org)
  • In type C, there is a defect in how fats (lipids) are moved around in a cell, resulting in accumulation of cholesterol and other fatty substances. (msdmanuals.com)
  • I made this video for World Rare Disease Day 2008 to bring global attention to the fact that Rare Disease is not so rare - it can happen to anyone or any family. (addiandcassi.com)
  • This was an awesome opportunity for our disease community to help spread awareness about this rare disease and hopefully attract the right people that help change the course of this. (bripardun.com)
  • IntraBio is preparing to initiate clinical trials with IB1001 for other rare and neurodegenerative diseases. (inpda.org)
  • Two cases of Niemann-Pick disease type C are described in order to illustrate the variable neurological features of this rare condition. (wiley.com)
  • Rare Disease PHGKB is an online, continuously updated, searchable database of published scientific literature, CDC and NIH resources, and other information that address the public health impact and translation of genomic and other precision health discoveries into improved health outcomes related to rare diseases. (cdc.gov)
  • Late onset of a metabolic disease is often triggered by acute metabolic stresses, such as infection, fasting, or consumption of a nutrient for which a metabolic intolerance exists. (newworldencyclopedia.org)