Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As our understanding of the genetic basis for inherited retinal disease has expanded, gene therapy has advanced into clinical development. When the gene mutations associated with inherited retinal dystrophies were identified, it became possible to create animal models in which individual gene were altered to match the human mutations. The retina of these animals were then characterized to assess whether the mutated genes produced retinal phenotypes characteristic of disease-affected patients. Following the identification of a subpopulation of patients with the affected gene and the development of techniques for the viral gene transduction of retinal cells, it has become possible to deliver a copy of the normal gene into the retinal sites of the mutated genes. When this was performed in animal models of monogenic diseases, at an early stage of retinal degeneration when the affected cells remained viable, successful gene augmentation corrected the structural and functional lesions characteristic of the specific diseases in the areas of the retina that were successfully transduced. These studies provided the essential proof-of-concept needed to advance monogenic gene therapies into clinic development; these therapies include treatments for: Leber's congenital amaurosis type 2, caused by mutations to RPE65, retinoid isomerohydrolase; choroideremia, caused by mutations to REP1, Rab escort protein 1; autosomal recessive Stargardt disease, caused by mutations to ABCA4, the photoreceptor-specific ATP-binding transporter; Usher 1B disease caused by mutations to MYO7A, myosin heavy chain 7; X-linked juvenile retinoschisis caused by mutations to RS1, retinoschisin; autosomal recessive retinitis pigmentosa caused by mutations to MERTK, the proto-oncogene tyrosine-protein kinase MER; Leber's hereditary optic neuropathy caused by mutations to ND4, mitochondrial nicotinamide adenine dinucleotide ubiquinone oxidoreductase (complex I) subunit 4 and achromatopsia, caused by mutations to CNGA3, cyclic nucleotide-gated channel alpha 3 and CNGB3, cyclic nucleotide-gated channel beta 3. This review includes a tabulated summary of treatments for these monogenic retinal dystrophies that have entered into clinical development, as well as a brief summary of the preclinical data that supported their advancement into clinical development.
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PMID:Hereditary Retinal Dystrophy. 2803 29

Precision medicine seeks to treat disease with molecular specificity. Advances in genome sequence analysis, gene delivery, and genome surgery have allowed clinician-scientists to treat genetic conditions at the level of their pathology. As a result, progress in treating retinal disease using genetic tools has advanced tremendously over the past several decades. Breakthroughs in gene delivery vectors, both viral and nonviral, have allowed the delivery of genetic payloads in preclinical models of retinal disorders and have paved the way for numerous successful clinical trials. Moreover, the adaptation of CRISPR-Cas systems for genome engineering have enabled the correction of both recessive and dominant pathogenic alleles, expanding the disease-modifying power of gene therapies. Here, we highlight the translational progress of gene therapy and genome editing of several retinal disorders, including RPE65-, CEP290-, and GUY2D-associated Leber congenital amaurosis, as well as choroideremia, achromatopsia, Mer tyrosine kinase- (MERTK-) and RPGR X-linked retinitis pigmentosa, Usher syndrome, neovascular age-related macular degeneration, X-linked retinoschisis, Stargardt disease, and Leber hereditary optic neuropathy.
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PMID:Gene therapy and genome surgery in the retina. 2985 67

Unlike rod monochromatism, which is an autosomal recessive disease that affects all three types of cones, blue cone monochromatism (BCM) is an X-linked disease that affects only L-cones and M-cones. The rods and S-cones are normal. The estimated prevalence is 1 in 100,00 individuals.
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PMID:Blue Cone Monochromatism. 3057 87

Rapid progress in knowledge of the organization of the dog genome has facilitated the identification of the mutations responsible for numerous monogenic diseases, which usually present a breed-specific distribution. The majority of these diseases have clinical and molecular counterparts in humans. The affected dogs have thus become valuable models for preclinical studies of gene therapy for problems such as eye diseases, immunodeficiency, lysosomal storage diseases, hemophilia, and muscular dystrophy. Successful gene therapies in dogs have significantly contributed to decisions to run clinical trials for several human diseases, such as Leber's congenital amaurosis 2-LCA2 (caused by a mutation of RPE65), X-linked retinitis pigmentosa-XLRP (caused by mutation RPGR), and achromatopsia (caused by mutation of CNGB3). Promising results were also obtained for canine as follows: hemophilia (A and B), mucopolysaccharidoses (MPS I, MPS IIIB, MPS VII), leukocyte adhesion deficiency (CLAD), and muscular dystrophy (a counterpart of human Duchenne dystrophy). Present knowledge on molecular background of canine monogenic diseases and their successful gene therapies prove that dogs have an important contribution to preclinical studies.
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PMID:Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. 3218 22


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