Choroideremia
Chromosome Walking
Alkyl and Aryl Transferases
Stapes
rab GTP-Binding Proteins
X Chromosome
Protein Prenylation
Hypohidrosis
Adaptor Proteins, Signal Transducing
Choroid
Retinal Degeneration
Molecular basis for Rab prenylation. (1/54)
Rab escort proteins (REP) 1 and 2 are closely related mammalian proteins required for prenylation of newly synthesized Rab GTPases by the cytosolic heterodimeric Rab geranylgeranyl transferase II complex (RabGG transferase). REP1 in mammalian cells is the product of the choroideremia gene (CHM). CHM/REP1 deficiency in inherited disease leads to degeneration of retinal pigmented epithelium and loss of vision. We now show that amino acid residues required for Rab recognition are critical for function of the yeast REP homologue Mrs6p, an essential protein that shows 50% homology to mammalian REPs. Mutant Mrs6p unable to bind Rabs failed to complement growth of a mrs6Delta null strain and were found to be dominant inhibitors of growth in a wild-type MRS6 strain. Mutants were identified that did not affect Rab binding, yet prevented prenylation in vitro and failed to support growth of the mrs6Delta null strain. These results suggest that in the absence of Rab binding, REP interaction with RabGG transferase is maintained through Rab-independent binding sites, providing a molecular explanation for the kinetic properties of Rab prenylation in vitro. Analysis of the effects of thermoreversible temperature-sensitive (mrs6(ts)) mutants on vesicular traffic in vivo showed prenylation activity is only transiently required to maintain normal growth, a result promising for therapeutic approaches to disease. (+info)Rab27a regulates the peripheral distribution of melanosomes in melanocytes. (2/54)
Rab GTPases are regulators of intracellular membrane traffic. We report a possible function of Rab27a, a protein implicated in several diseases, including Griscelli syndrome, choroideremia, and the Hermansky-Pudlak syndrome mouse model, gunmetal. We studied endogenous Rab27a and overexpressed enhanced GFP-Rab27a fusion protein in several cultured melanocyte and melanoma-derived cell lines. In pigmented cells, we observed that Rab27a decorates melanosomes, whereas in nonpigmented cells Rab27a colocalizes with melanosome-resident proteins. When dominant interfering Rab27a mutants were expressed in pigmented cells, we observed a redistribution of pigment granules with perinuclear clustering. This phenotype is similar to that observed by others in melanocytes derived from the ashen and dilute mutant mice, which bear mutations in the Rab27a and MyoVa loci, respectively. We also found that myosinVa coimmunoprecipitates with Rab27a in extracts from melanocytes and that both Rab27a and myosinVa colocalize on the cytoplasmic face of peripheral melanosomes in wild-type melanocytes. However, the amount of myosinVa in melanosomes from Rab27a-deficient ashen melanocytes is greatly reduced. These results, together with recent data implicating myosinVa in the peripheral capture of melanosomes, suggest that Rab27a is necessary for the recruitment of myosinVa, so allowing the peripheral retention of melanosomes in melanocytes. (+info)Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease. (3/54)
Small GTPases of the Rab family regulate membrane transport pathways. More than 50 mammalian Rab proteins are known, many with transport step-specific localisation. Rabs must associate with cellular membranes for activity and membrane attachment is mediated by prenyl (geranylgeranyl) post-translational modification. Mutations in genes encoding proteins essential for the geranylgeranylation reaction, Rab escort protein and Rab geranylgeranyl transferase, underlie genetic diseases. Choroideremia patients have loss of function mutations in REP1 and the murine Hermansky-Pudlak syndrome model gunmetal possesses a splice-site mutation in the alpha-subunit of RGGT. Here we discuss recent insights into Rab prenylation and advances towards our understanding of both diseases. (+info)Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia. (4/54)
BACKGROUND/AIMS: Few studies have reported on the change in visual acuity (VA) in patients with choroideraemia. In order to determine the degree and rate of VA impairment associated with this disease, the central VA was analysed in a large group of patients with choroideraemia. METHODS: The authors completed a retrospective, cross sectional review of 115 patients with choroideraemia from three tertiary care centres. A longitudinal analysis was performed on 45 of these patients who met the inclusion criteria of at least three visits over a minimum period of 4.5 years. Multiple linear regression analysis was used to explore the 5 year rate of VA change while controlling for initial VA and initial age. Multiple logistic regression was also used to investigate VA impairment. RESULTS: In the cross sectional group (n = 115), 84% (87/103) of patients under the age of 60 had a VA of 20/40 or better while 33% (4/12) of patients 60 years of age or older had a VA of 20/200 or worse at their most recent visit. The majority of the patients (93%) in the longitudinal subgroup of 45 patients had a VA of 20/30 or better at their initial visit. The mean 5 year rate of VA change was 0.09 logMAR equivalent (approximately one line on the Lighthouse chart). CONCLUSION: In this cohort of patients with choroideraemia, there was typically a slow rate of VA loss and the prognosis for central VA retention was, as a group, favourable until the seventh decade. (+info)Rapid degradation of dominant-negative Rab27 proteins in vivo precludes their use in transgenic mouse models. (5/54)
BACKGROUND: Transgenic mice have proven to be a powerful system to study normal and pathological gene functions. Here we describe an attempt to generate a transgenic mouse model for choroideremia (CHM), a slow-onset X-linked retinal degeneration caused by mutations in the Rab Escort Protein-1 (REP1) gene. REP1 is part of the Rab geranylgeranylation machinery, a modification that is essential for Rab function in membrane traffic. The loss of REP1 in CHM patients may trigger retinal degeneration through its effects on Rab proteins. We have previously reported that Rab27a is the Rab most affected in CHM lymphoblasts and hypothesised that the selective dysfunction of Rab27a (and possibly a few other Rab GTPases) plays an essential role in the retinal degenerative process. RESULTS: To investigate this hypothesis, we generated several lines of dominant-negative, constitutively-active and wild-type Rab27a (and Rab27b) transgenic mice whose expression was driven either by the pigment cell-specific tyrosinase promoter or the ubiquitous beta-actin promoter. High levels of mRNA and protein were observed in transgenic lines expressing wild-type or constitutively active Rab27a and Rab27b. However, only modest levels of transgenic protein were expressed. Pulse-chase experiments suggest that the dominant-negative proteins, but not the constitutively-active or wild type proteins, are rapidly degraded. Consistently, no significant phenotype was observed in our transgenic lines. Coat-colour was normal, indicating normal Rab27a activity. Retinal function as determined by fundoscopy, angiography, electroretinography and histology was also normal. CONCLUSIONS: We suggest that the instability of the dominant-negative mutant Rab27 proteins in vivo precludes the use of this approach to generate mouse models of disease caused by Rab27 GTPases. (+info)Gene therapy for choroideremia: in vitro rescue mediated by recombinant adenovirus. (6/54)
Choroideremia (CHM) is an X-linked retinal degenerative disease resulting from a lack of functional Rab Escort Protein-1 (REP-1). As a first step in developing gene-based therapies for this disease, we evaluated the feasibility of delivering functional REP-1 to defective lymphocytes and fibroblasts isolated from individuals with CHM. A recombinant adenovirus delivering the full-length human cDNA encoding REP-1 under the control of a cytomegalovirus promoter was generated. Adenovirus-mediated delivery of REP-1 rescued the defective cells as assessed through protein and enzymatic assays. Ultimately, it may be possible to use virus-mediated delivery of REP-1 to evaluate disease intervention in vivo. (+info)A case of choroideremia with recurrent anterior uveitis. (7/54)
Choroideremia is a rare hereditary disease with characteristic fundus that causes night blindness and peripheral visual field loss. The authors encounter choroideremia accompanied by recurrent uveitis. This paper is designed to give a description of the condition, along with an investigation of the literature. Ophthalmological tests and treatments were performed. Characteristic fundus, night blindness, peripheral visual field loss, electroretinography and other manifestations led us to a diagnosis of choroideremia. The anterior uveitis was managed with medication. (+info)Multiple factors contribute to inefficient prenylation of Rab27a in Rab prenylation diseases. (8/54)
Post-translational geranylgeranylation of Rab GT-Pases is essential for their membrane association and function as regulators of intracellular vesicular transport. The reaction is catalyzed by Rab geranylgeranyltransferase (RGGT) and is assisted by the Rab escort proteins (REP), which form stable complexes with newly synthesized GDP-bound Rabs. Two genetic diseases involve the Rab geranylgeranylation machinery: choroideremia, an X-linked retinal degeneration resulting from loss-of-function mutations in REP1, and gunmetal, a mouse model of Hermansky-Pudlak syndrome resulting from mutations in the alpha-subunit of RGGT. A small subset of Rab proteins is selectively under-prenylated in both diseases, most notably Rab27a. Here we analyze why Rab27a is selectively affected in diseases of Rab geranylgeranylation. Semi-quantitative immunoblotting suggests that mass action, i.e. the amount of Rab27a relative to other Rabs, is unlikely to be a factor as the expression level of Rab27a is similar to other Rabs not affected in these diseases. In vitro binding assays and fluorescence resonance energy transfer detected by fluorescence lifetime imaging microscopy in intact cells demonstrate that Rab27a binds equally well to both REP1 and REP2, suggesting differential affinity of Rab27a for REP isoforms is not an important factor. However, steady-state kinetic analysis of the geranylgeranylation reaction indicates that REP2-Rab27a has lower affinity for RGGT compared with REP1-Rab27a. Furthermore, we show that Rab27a has relatively low GTPase activity, presumably decreasing the affinity of the REP interaction in vivo. We suggest that the restricted phenotypes observed in these diseases result from multiple contributing factors. (+info)Choroideremia is a rare inherited eye disorder that causes progressive loss of vision. It primarily affects the choroid, which is the layer of blood vessels that provides oxygen and nutrients to the outer layers of the retina. The disease also damages the retina and the optic nerve over time.
The condition is caused by mutations in the CHM gene, which provides instructions for making a protein called REP-1 that is essential for maintaining the health of the light-sensitive cells in the retina (rods and cones). Without this protein, these cells gradually deteriorate and die, leading to vision loss.
Choroideremia typically affects males more severely than females, and it usually begins in childhood with night blindness (nyctalopia) and decreased visual acuity. Over time, the field of vision becomes narrower (tunnel vision), and eventually, complete blindness can occur. Currently, there is no cure for choroideremia, but research is ongoing to develop potential treatments such as gene therapy.
Uveal diseases refer to a group of medical conditions that affect the uvea, which is the middle layer of the eye located between the sclera (the white of the eye) and the retina (the light-sensitive tissue at the back of the eye). The uvea consists of the iris (the colored part of the eye), the ciliary body (which controls the lens), and the choroid (a layer of blood vessels that provides nutrients to the retina).
Uveal diseases can cause inflammation, damage, or tumors in the uvea, leading to symptoms such as eye pain, redness, light sensitivity, blurred vision, and floaters. Some common uveal diseases include uveitis (inflammation of the uvea), choroidal melanoma (a type of eye cancer that affects the choroid), and iris nevus (a benign growth on the iris). Treatment for uveal diseases depends on the specific condition and may include medications, surgery, or radiation therapy.
Chromosome walking is a historical term used in genetics to describe the process of mapping and sequencing DNA along a chromosome. It involves the identification and characterization of a specific starting point, or "landmark," on a chromosome, followed by the systematic analysis of adjacent DNA segments, one after another, in a step-by-step manner.
The technique typically employs the use of molecular biology tools such as restriction enzymes, cloning vectors, and genetic markers to physically isolate and characterize overlapping DNA fragments that cover the region of interest. By identifying shared sequences or markers between adjacent fragments, researchers can "walk" along the chromosome, gradually building up a more detailed map of the genetic sequence.
Chromosome walking was an important technique in the early days of genetics and genomics research, as it allowed scientists to systematically analyze large stretches of DNA before the advent of high-throughput sequencing technologies. Today, while whole-genome sequencing has largely replaced chromosome walking for many applications, the technique is still used in some specialized contexts where a targeted approach is required.
Alkyl and aryl transferases are a group of enzymes that catalyze the transfer of alkyl or aryl groups from one molecule to another. These enzymes play a role in various biological processes, including the metabolism of drugs and other xenobiotics, as well as the biosynthesis of certain natural compounds.
Alkyl transferases typically catalyze the transfer of methyl or ethyl groups, while aryl transferases transfer larger aromatic rings. These enzymes often use cofactors such as S-adenosylmethionine (SAM) or acetyl-CoA to donate the alkyl or aryl group to a recipient molecule.
Examples of alkyl and aryl transferases include:
1. Methyltransferases: enzymes that transfer methyl groups from SAM to various acceptor molecules, such as DNA, RNA, proteins, and small molecules.
2. Histone methyltransferases: enzymes that methylate specific residues on histone proteins, which can affect chromatin structure and gene expression.
3. N-acyltransferases: enzymes that transfer acetyl or other acyl groups to amino groups in proteins or small molecules.
4. O-acyltransferases: enzymes that transfer acyl groups to hydroxyl groups in lipids, steroids, and other molecules.
5. Arylsulfatases: enzymes that remove sulfate groups from aromatic rings, releasing an alcohol and sulfate.
6. Glutathione S-transferases (GSTs): enzymes that transfer the tripeptide glutathione to electrophilic centers in xenobiotics and endogenous compounds, facilitating their detoxification and excretion.
The stapes is the smallest bone in the human body, which is a part of the middle ear. It is also known as the "stirrup" because of its U-shaped structure. The stapes connects the inner ear to the middle ear, transmitting sound vibrations from the ear drum to the inner ear. More specifically, it is the third bone in the series of three bones (the ossicles) that conduct sound waves from the air to the fluid-filled inner ear.
Rab GTP-binding proteins, also known as Rab GTPases or simply Rabs, are a large family of small GTP-binding proteins that play a crucial role in regulating intracellular vesicle trafficking. They function as molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state.
In the active state, Rab proteins interact with various effector molecules to mediate specific membrane trafficking events such as vesicle budding, transport, tethering, and fusion. Each Rab protein is thought to have a unique function and localize to specific intracellular compartments or membranes, where they regulate the transport of vesicles and organelles within the cell.
Rab proteins are involved in several important cellular processes, including endocytosis, exocytosis, Golgi apparatus function, autophagy, and intracellular signaling. Dysregulation of Rab GTP-binding proteins has been implicated in various human diseases, such as cancer, neurodegenerative disorders, and infectious diseases.
The X chromosome is one of the two types of sex-determining chromosomes in humans (the other being the Y chromosome). It's one of the 23 pairs of chromosomes that make up a person's genetic material. Females typically have two copies of the X chromosome (XX), while males usually have one X and one Y chromosome (XY).
The X chromosome contains hundreds of genes that are responsible for the production of various proteins, many of which are essential for normal bodily functions. Some of the critical roles of the X chromosome include:
1. Sex Determination: The presence or absence of the Y chromosome determines whether an individual is male or female. If there is no Y chromosome, the individual will typically develop as a female.
2. Genetic Disorders: Since females have two copies of the X chromosome, they are less likely to be affected by X-linked genetic disorders than males. Males, having only one X chromosome, will express any recessive X-linked traits they inherit.
3. Dosage Compensation: To compensate for the difference in gene dosage between males and females, a process called X-inactivation occurs during female embryonic development. One of the two X chromosomes is randomly inactivated in each cell, resulting in a single functional copy per cell.
The X chromosome plays a crucial role in human genetics and development, contributing to various traits and characteristics, including sex determination and dosage compensation.
Protein prenylation is a post-translational modification process in which a lipophilic group, such as a farnesyl or geranylgeranyl moiety, is covalently attached to specific cysteine residues near the carboxy-terminus of proteins. This modification plays a crucial role in membrane targeting and protein-protein interactions, particularly for proteins involved in signal transduction pathways, such as Ras family GTPases. The enzymes responsible for prenylation are called protein prenyltransferases, and their dysfunction has been implicated in various diseases, including cancer and neurodegenerative disorders.
Hypohidrosis is a medical condition characterized by reduced or absent sweating. It's the opposite of hyperhidrosis, which is excessive sweating. Sweating is an essential function that helps regulate body temperature through the evaporation of sweat on the skin surface. When this process is impaired due to hypohidrosis, it can lead to difficulties in maintaining a normal body temperature, especially during physical exertion or in hot environments.
Hypohidrosis may be localized, affecting only certain areas of the body, or generalized, affecting the entire body. The causes of hypohidrosis are varied and include genetic factors, nerve damage, skin disorders, dehydration, burns, or the use of certain medications. Depending on its underlying cause, hypohidrosis can be managed through appropriate treatments, such as addressing nerve damage, managing skin conditions, or adjusting medication usage.
Adaptor proteins are a type of protein that play a crucial role in intracellular signaling pathways by serving as a link between different components of the signaling complex. Specifically, "signal transducing adaptor proteins" refer to those adaptor proteins that are involved in signal transduction processes, where they help to transmit signals from the cell surface receptors to various intracellular effectors. These proteins typically contain modular domains that allow them to interact with multiple partners, thereby facilitating the formation of large signaling complexes and enabling the integration of signals from different pathways.
Signal transducing adaptor proteins can be classified into several families based on their structural features, including the Src homology 2 (SH2) domain, the Src homology 3 (SH3) domain, and the phosphotyrosine-binding (PTB) domain. These domains enable the adaptor proteins to recognize and bind to specific motifs on other signaling molecules, such as receptor tyrosine kinases, G protein-coupled receptors, and cytokine receptors.
One well-known example of a signal transducing adaptor protein is the growth factor receptor-bound protein 2 (Grb2), which contains an SH2 domain that binds to phosphotyrosine residues on activated receptor tyrosine kinases. Grb2 also contains an SH3 domain that interacts with proline-rich motifs on other signaling proteins, such as the guanine nucleotide exchange factor SOS. This interaction facilitates the activation of the Ras small GTPase and downstream signaling pathways involved in cell growth, differentiation, and survival.
Overall, signal transducing adaptor proteins play a critical role in regulating various cellular processes by modulating intracellular signaling pathways in response to extracellular stimuli. Dysregulation of these proteins has been implicated in various diseases, including cancer and inflammatory disorders.
The choroid is a layer of the eye that contains blood vessels that supply oxygen and nutrients to the outer layers of the retina. It lies between the sclera (the white, protective coat of the eye) and the retina (the light-sensitive tissue at the back of the eye). The choroid is essential for maintaining the health and function of the retina, particularly the photoreceptor cells that detect light and transmit visual signals to the brain. Damage to the choroid can lead to vision loss or impairment.
Retinal degeneration is a broad term that refers to the progressive loss of photoreceptor cells (rods and cones) in the retina, which are responsible for converting light into electrical signals that are sent to the brain. This process can lead to vision loss or blindness. There are many different types of retinal degeneration, including age-related macular degeneration, retinitis pigmentosa, and Stargardt's disease, among others. These conditions can have varying causes, such as genetic mutations, environmental factors, or a combination of both. Treatment options vary depending on the specific type and progression of the condition.
"Fundus Oculi" is a medical term that refers to the back part of the interior of the eye, including the optic disc, macula, fovea, retinal vasculature, and peripheral retina. It is the area where light is focused and then transmitted to the brain via the optic nerve, forming visual images. Examinations of the fundus oculi are crucial for detecting various eye conditions such as diabetic retinopathy, macular degeneration, glaucoma, and other retinal diseases. The examination is typically performed using an ophthalmoscope or a specialized camera called a retinal camera.
Choroideremia
List of OMIM disorder codes
Ayazi syndrome
Rab escort protein 1
RAB27A
Robert MacLaren
Gene therapy of the human retina
Rab (G-protein)
CHML (gene)
Spark Therapeutics
Ludwig Mauthner
RAB6A
RAB1A
RAB3A
RAB5A
Siôn Simon
Michael Stuart Brown
Albert de la Chapelle
Mark Huyser-Wierenga
Gene therapy
Deborah Ann Woll
Shapiro Senapathy algorithm
Sam Harding (athlete)
John-Ross Rizzo
Prenylation
List of diseases (C)
Eye disease
Finnish heritage disease
Foundation Fighting Blindness
Nyctalopia
Choroideremia - Wikipedia
Choroideremia: MedlinePlus Genetics
Clinical and genetic findings in a Chinese cohort with choroideremia | Eye
Choroideremia Research Foundation. | Celeb Dirty Laundry
4D-110 by 4D Molecular Therapeutics for Choroideremia: Likelihood of Approval
CRISPR-Based Gene editing for Choroideremia | Champalimaud Foundation
CRF STRENGTHENS COMMITMENT TO FIND A CURE FOR CHOROIDEREMIA A RARE INHERETED RETINAL DISEASE THAT CAUSES BLINDNESS - EIN...
choroideremia research Archives - CureCHM
CHOROIDEREMIA RESEARCH FOUNDATION STRENGTHENS LEADERSHIP - CureCHM
Novel imaging approach reveals important details about rare eye disease choroideremia - Florida Hospital News and Healthcare...
ProjectCHM (Choroideremia) | The John and Marcia Carver Nonprofit Genetic Testing Laboratory
Choroideremia - Retina Image Bank
Choroideremia funding - The Geeked Gods
Choroidal Thickness in Choroideremia - Oxford Neuroscience
Choroid eremia<...
Low-contrast visual acuity versus low-luminance visual acuity in choroideremia - Nuffield Department of Primary Care Health...
Characterizing the Natural History of Visual Function in Choroideremia Using Microperimetry and Multimodal Retinal Imaging -...
Choroideremia With Periperal Pigment Changes, Drusenoid Flecks, Patchy Atrophy - Retina Image Bank
Gene therapy for choroideremia using an adeno-associated viral (AAV) vector. - Oxford Neuroscience
BioWorld
Clinical and Translational Imaging Section | National Eye Institute
Long term vision results following retinal gene therapy for choroideremia - Wellcome Centre for Integrative Neuroimaging
Chromosome 9 News, Research - Page 3
VASCULAR ALTERATIONS REVEALED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH CHOROIDEREMIA. - Oxford Stem Cell...
Retinitis Pigmentosa: Practice Essentials, Background, Pathophysiology
Assessment of the relationship between CHM gene expression and rate of disease progression in choroideremia - Wellcome Centre...
Functional expression of Rab escort protein 1 following AAV2-mediated gene delivery in the retina of choroideremia mice and...
Choroideremia Pipeline Drugs and Companies Insight Report, 2023 Updates: Analysis of Clinical Trials, Therapies, Mechanism of...
Diagnosis of choroideremia3
- A diagnosis of choroideremia can be made based on family history, symptoms and the characteristic appearance of the fundus. (wikipedia.org)
- Mutational analysis of patients with the diagnosis of choroideremia. (medlineplus.gov)
- A New York physician hasn't let a diagnosis of choroideremia stop him from fulfilling his dreams. (medicaleconomics.com)
Gene therapy for choroideremia2
- Pathogenic mechanisms and the prospect of gene therapy for choroideremia. (nature.com)
- Gene therapy for choroideremia using an adeno-associated viral (AAV) vector. (ox.ac.uk)
Genetic7
- However, choroideremia shares several clinical features with retinitis pigmentosa, a similar but broader group of retinal degenerative diseases, making a specific diagnosis difficult without genetic testing. (wikipedia.org)
- By combining traditional eye imaging techniques with adaptive optics - a technology that enhances imaging resolution - researchers at the National Eye Institute (NEI) have shown for the first time how cells across different tissue layers in the eye are affected in people with choroideremia, a rare genetic disorder that leads to blindness. (southfloridahospitalnews.com)
- ProjectCHM seeks to identify every person in the United States affected with choroideremia and offer them state of the art genetic testing on a nonprofit basis through the John and Marcia Carver Nonprofit Genetic Testing Laboratory at the University of Iowa. (carverlab.org)
- Make a genetic test for choroideremia available to all who might benefit from one. (carverlab.org)
- Many insurance companies are currently unfamiliar with the value of genetic testing for choroideremia. (carverlab.org)
- As a result, genetic testing will become part of the "standard of care" for choroideremia in the United States. (carverlab.org)
- Choroideremia is a rare genetic disorder of vision that is more common in man. (giridihjournal.in)
Retina1
- Loss of REP-1 function and subsequent misplacement of Rab proteins within the cells of the retina causes the progressive vision loss characteristic of choroideremia. (medlineplus.gov)
Retinal disease3
- The CRF has funded more than $4 million in scientific research for a treatment and/or cure for choroideremia (CHM), a rare and inherited retinal disease that causes visual impairment and potentially complete blindness. (einnews.com)
- Choroideremia is a slowly progressive inherited retinal disease caused by recessive mutations of the CHM gene that lies on the long arm of the X-chromosome. (carverlab.org)
- PURPOSE: Choroideremia is a rare degenerative retinal disease that causes incurable blindness. (ox.ac.uk)
Recessive2
- Choroideremia is inherited in an X-linked recessive pattern . (medlineplus.gov)
- Choroideremia shows X-linked recessive inheritance and the choroideremia gene (CHM) was one of the first to be identified by positional cloning in 1990. (ox.ac.uk)
Therapeutics3
- 4D-110 is under clinical development by 4D Molecular Therapeutics and currently in Phase II for Choroideremia. (pharmaceutical-technology.com)
- Key companies developing therapies for Choroideremia are - NightstaRx Ltd/Biogen, 4D Molecular Therapeutics, Curative Biotech, Therapeutics, Spark therapeutics/Roche, and others. (giridihjournal.in)
- For instance, Spark Therapeutics, Inc. has SPK-7001 (Choroideremia/ Phase ½), SPK-8011 (Hemophilia A/Phase ½), and SPK-3006 (Pompe Disease/preclinical) in the pipeline. (medgadget.com)
Diseases2
- His team was able to see in detail the extent to which choroideremia disrupts these tissues, providing information that could help design effective treatments for this and other diseases. (southfloridahospitalnews.com)
- Defects in Rab27A function are associated with the human diseases choroideremia and Griscelli syndrome 2 and the ashen mutant mouse. (bdbiosciences.com)
Atrophy1
- Choroideremia and gyrate atrophy are examples of this type of dystrophy. (rnib.org.uk)
Retinitis1
- Because of this choroideremia is often initially misdiagnosed as retinitis pigmentosa. (wikipedia.org)
Adaptive optics1
- Using adaptive optics to image RPE cells in choroideremia. (aao.org)
Characteristic1
- Choroideremia is an outer retinal degeneration with a characteristic clinical appearance that was first described in the nineteenth century. (ox.ac.uk)
Thrilled to announce1
- SPRINGFIELD, MA, UNITED STATES, January 4, 2022 / EINPresswire.com / -- The Choroideremia Research Foundation (CRF) is thrilled to announce the expansion of its prestigious Scientific Advisory Board with the addition of Maureen McCall, Ph.D. Dr. McCall is Professor & Vice Chair of Research for the Department of Ophthalmology and Visual Sciences at the University of Louisville (Kentucky). (einnews.com)
Clinical features1
- Encouragingly, several specific molecular and clinical features make choroideremia an ideal candidate for treatment with gene therapy. (ox.ac.uk)
Mutations3
- Mutations in the CHM gene cause choroideremia. (medlineplus.gov)
- The spectrum of CHM gene mutations in choroideremia and their relationship to clinical phenotype. (nature.com)
- By collecting some basic clinical information from thousands of people affected with choroideremia, doctors will be able to discern the clinical severity associated with specific mutations in the CHM gene and will be able to use this information to give newly diagnosed individuals and their families more accurate information about what to expect. (carverlab.org)
Incurable1
- John-Ross Rizzo, MD, took that phrase to heart when, at age 15, he was diagnosed with choroideremia, a progressive and incurable disease from which he is losing his vision. (medicaleconomics.com)
Slowly progressive1
- A movie called Saving Sight detailed the fight to develop a treatment for a slowly-progressive eye disorder called choroideremia. (rareshare.org)
Vector3
- In the study, 2 doses of the AAV.REP1 vector were injected subretinally in 12 patients with choroideremia. (wikipedia.org)
- The therapy is based on vector evolution platform technology that uses AAV2 (Adeno-Associated Virus2) vector variant carrying a transgene encoding a codon-optimized human choroideremia (CHM) gene. (pharmaceutical-technology.com)
- Evaluation of CRISPR/Cas9 exon-skipping vector for choroideremia using human induced pluripotent stem cell-derived RPE. (nih.gov)
Trials6
- Gene therapy is currently not a treatment option, however human clinical trials for both choroideremia and Leber's congenital amaurosis (LCA) have produced somewhat promising results. (wikipedia.org)
- Analysis of a large choroideremia dataset does not suggest a preference for inclusion of certain genotypes in future trials of gene therapy. (nature.com)
- The outcomes of viral-mediated gene therapy trials in Ophthalmology, including Choroideremia, have uncovered some unforeseen problems, such as the most recent Phase III clinical trial sponsored by Biogen, which failed to meet the endpoints. (fchampalimaud.org)
- Trials of new treatments for choroideremia will require access to molecularly confirmed individuals affected with the disease. (carverlab.org)
- This study assesses whether low‐luminance visual acuity and low‐contrast visual acuity provide useful endpoints in choroideremia clinical trials. (ox.ac.uk)
- Las Vega (Nevada), United States //- As per DelveInsight's assessment, globally, Choroideremia pipeline constitutes 5+ key companies continuously working towards developing 5+ Choroideremia treatment therapies, analysis of Clinical Trials, Therapies, Mechanism of Action, Route of Administration, and Developments analyzes DelveInsight. (giridihjournal.in)
100,0002
- The prevalence of choroideremia is estimated to be 1 in 50,000 to 100,000 people. (medlineplus.gov)
- Choroideremia is estimate to occur in 1/100,000 individuals in the general population. (carverlab.org)
Treatments2
- There are currently no approved treatments for Choroideremia. (einnews.com)
- Despite several decades of work to understand the exact pathogenesis, no established treatments currently exist to stop or even slow the progression of retinal degeneration in choroideremia. (ox.ac.uk)
Affects3
- Choroideremia is a condition characterized by progressive vision loss that mainly affects males. (medlineplus.gov)
- Choroideremia affects men more than women because the gene responsible for the disease is located on the X chromosome. (southfloridahospitalnews.com)
- So, it affects males and it's called choroideremia which is an original description given to it, well over 100 years ago. (thenakedscientists.com)
Viral1
- Only, rather than carrying the viral gene, the virus contains the choroideremia gene which we've artificially put into it. (thenakedscientists.com)
Progression1
- The vision impairment in choroideremia worsens over time, but the progression varies among affected individuals. (medlineplus.gov)
Rare2
- Choroideremia (CHM) is a rare inherited form of blindness affecting approximately 1 in 50,000 people. (einnews.com)
- CHOROIDEREMIA is a rare clinical entity. (eyehospital.nl)
Blindness1
- Choroideremia is thought to account for approximately 4 percent of all blindness. (medlineplus.gov)
Treatment4
- In 2011, the first gene therapy treatment for choroideremia was administered. (wikipedia.org)
- 4D-110 is under development for the treatment of choroideremia. (pharmaceutical-technology.com)
- Companies across the globe are diligently working toward developing novel Choroideremia treatment therapies with a considerable amount of success over the years. (giridihjournal.in)
- The report provides detailed insights about companies that are developing therapies for the treatment of Choroideremia with aggregate therapies developed by each company for the same. (giridihjournal.in)
Disease4
- The discovery of the gene that causes choroideremia (by Cremers and co-workers in 1990) and the availability of a relatively inexpensive test for disease-causing alterations in this gene are both sufficiently new that most affected individuals and many eye doctors are currently unaware that such testing exists. (carverlab.org)
- Many individuals affected with choroideremia have been told directly or indirectly that "there is nothing that can be done" to arrest the disease or improve their vision. (carverlab.org)
- Project CHM seeks to reverse this message and make it clear that there is much that the individuals with choroideremia can do as a group to help combat this disease. (carverlab.org)
- CONCLUSION: Choroideremia is a disease in which the choriocapillaris maintains a normal structure until the loss of the overlying retinal pigment epithelium. (ox.ac.uk)
Males1
- One major finding of our study was that the RPE cells are dramatically enlarged in males and females with choroideremia," said Tam. (southfloridahospitalnews.com)
Symptoms1
- This may explain why women with choroideremia have milder symptoms, according to Tam. (southfloridahospitalnews.com)
Research Foundation5
- Choroideremia Research Foundation. (celebdirtylaundry.com)
- Posts tagged as 'Choroideremia Research Foundation. (celebdirtylaundry.com)
- About the Choroideremia Research Foundation Inc. (einnews.com)
- The Choroideremia Research Foundation was founded in 2000 as an international fundraising and patient advocacy organization to stimulate research on CHM. (einnews.com)
- The Choroideremia Research Foundation (CRF) is pleased to announce the appointment of four new members to its board of directors. (curechm.org)
Drugs2
- According to GlobalData, Phase II drugs for Choroideremia does not have sufficient historical data to build an indication benchmark PTSR for Phase II. (pharmaceutical-technology.com)
- Choroideremia pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. (giridihjournal.in)
Patients4
- A study of 115 individuals with choroideremia found that 84% of patients under the age of 60 had a visual acuity of 20/40 or better, while 33% of patients over 60 years old had a visual acuity of 20/200 or worse. (wikipedia.org)
- One study found that a dietary supplement of lutein increases macular pigment levels in patients with choroideremia. (wikipedia.org)
- CHM/REP1 transcript expression and loss of visual function in patients affected by choroideremia. (nature.com)
- Robert - Well, the patients have this retinal degeneration because they're missing the choroideremia gene, or the CHM gene for short. (thenakedscientists.com)
Vision1
- The first symptom many individuals with choroideremia notice is a significant loss of night vision, which begins in youth. (wikipedia.org)
People1
- An estimated 6,000 people in the United States and 10,000 in the European Union are impacted by Choroideremia. (einnews.com)
Make1
- In the case of choroideremia, what we do is we make a virus that carries DNA, because viruses do carry DNA or RNA, that's the property of virus. (thenakedscientists.com)
Visual3
- Individuals with choroideremia tend to maintain good visual acuity into their 40s, but eventually lose all sight at some point in the 50-70 age range. (wikipedia.org)
- Method: Standard high‐contrast and low‐luminance visual acuity was obtained on 29 choroideremia subjects and 16 healthy controls, using a logMAR chart, set at four metres. (ox.ac.uk)
- Results: A higher number of choroideremia subjects were able to complete the low‐luminance test than the low‐contrast visual acuity tests. (ox.ac.uk)
Function1
- Choroideremia is caused by a loss-of-function mutation in the CHM gene which encodes Rab escort protein 1 (REP1), a protein involved in lipid modification of Rab proteins. (wikipedia.org)
Cells2
- RPE cells (see circled examples) in a male participant with choroideremia, showing that enlarged RPE cells can be detected using Tam's multimodal imaging approach. (southfloridahospitalnews.com)
- But in fact, it is the choroideremia gene that goes into those cells. (thenakedscientists.com)
Women1
- Because women have two copies of the X-chromosome and men only have one, full blown choroideremia is much more common in men than in women. (carverlab.org)
Cure1
- The CRF awards three research grants totaling $219,000 to continue leading efforts to find a cure for Choroideremia Springfield, MA. (curechm.org)
Page1
- Additional information regarding choroideremia may be found at the Project CHM Resource Page . (carverlab.org)
Market2
- " Choroideremia Pipeline Insight, 2023 " report by DelveInsight outlines comprehensive insights into the present clinical development scenario and growth prospects across the Choroideremia Market. (giridihjournal.in)
- Choroideremia Emerging therapies such as - Metformin, 4D-110, SPK-7001, BIIB111 , and others are expected to have a significant impact on the Choroideremia market in the coming years. (giridihjournal.in)
Subjects1
- METHODS: Six men with choroideremia were identified and underwent standardized optical coherence tomography angiography as part of an ethics-approved clinical study and were compared with age-matched control subjects. (ox.ac.uk)