Some patients with achromatopsia, an inherited disorder characterized by partial or complete loss of color vision, carry mutations in ATF6. ATF6 is a gene that is responsible for coding a protein that acts in response to endoplasmic reticulum (ER) stress. When the ATF6 protein is mutated, retinal function decreases, contributing to color blindness. The study aims to investigate whether an already FDA-approved drug, glycerol phenylbutyrate (PBA), can improve retinal function inpatients with achromatopsia caused by ATF6 mutations. Patients will be instructed to take three doses of PBA per day at equally divided time intervals and rounded up to the nearest 0.5 mL. The total dose of PBA will be 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) and will not exceed 17.5 mL/day (19 g/day). Their condition will be monitored over the course of a minimum of 3 clinic visits that will consist of a number of retinal function tests, fundus examinations, and imaging procedures. Findings from the study could elucidate the potential for PBA to serve as a treatment for patients with ATF6-mediated a chromatopsia.

Start Date01 Dec 2024

Sponsor / Collaborator

Columbia University

NCT03758404 / CompletedPhase 1/2

An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/8-hG1.7p.coCNGA3) for Gene Therapy of Children and Adults With Achromatopsia Owing to Defects in CNGA3

A clinical trial of adeno-associated virus vector (AAV) CNGA3 retinal gene therapy for patients with achromatopsia

Start Date12 Aug 2019

Sponsor / Collaborator

MeiraGTx UK II Ltd.

[+1]

EUCTR2018-003431-29-GB / Unknown statusPhase 1/2

An open label, multi-centre, Phase I/II dose escalation trial of an adeno-associated virus vector (AAV2/8-hG1.7p.coCNGA3) for gene therapy of children with achromatopsia owing to defects in CNGA3 - Gene Therapy for Achromatopsia (CNGA3)

Start Date24 Jun 2019

Sponsor / Collaborator

MeiraGTx UK II Ltd.

100 Clinical Results associated with Achromatopsia 1

100 Translational Medicine associated with Achromatopsia 1

0 Patents (Medical) associated with Achromatopsia 1

605

Literatures (Medical) associated with Achromatopsia 1

04 Oct 2024·Investigative Ophthalmology & Visual Science

Longitudinal Imaging of the Foveal Cone Mosaic in CNGA3-Associated Achromatopsia

Article

Author: Michaelides, Michel ; Dubra, Alfredo ; Georgiou, Michalis ; Katta, Mohamed ; Carroll, Joseph ; Kalitzeos, Angelos ; Singh, Navjit

PurposeThe purpose of this study was to assess the natural history of the foveal cone mosaic in CNGA3-associated achromatopsia (ACHM).MethodsThirteen eyes from 10 genetically confirmed patients underwent longitudinal imaging with optical coherence tomography (OCT) and non-confocal split detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans assessed outer nuclear layer (ONL) thickness, foveal ellipsoid zone (EZ) disruption, and foveal hypoplasia. AOSLO images were analyzed to calculate peak foveal cone density (PCD) and mean inter-cell distance (ICD) between cones. Mixed effects models were used to analyze the rate of annual change of PCD and ICD.ResultsMean (±SD) age at visits was 29 ± 10 years, with a follow-up of 2.6 ± 1 years. There was no change in ONL thickness, degree of EZ disruption, or foveal hypoplasia over the follow-up period. We also observed a stable foveal cone mosaic using AOSLO imaging, with no significant change in PCD or ICD. Mean PCD was 15,346 cones/mm² at the mean age of 29 years old (cf. 64,000-324,000 cones/mm² in previously reported healthy controls), with a mean rate of change of -117.79 cones/mm² (0.8%) per year, P = 0.130. Mean ICD at the mean age was 13.82 µm, with a rate of change of 0.17 µm per year, P = 0.83.ConclusionsCNGA3-associated ACHM displays stable foveal cone structure over time with a similar rate of change to CNGB3-associated ACHM (2% decline per year). The stable PCD, small cohort, and large variability within the cohort means significant age associations were not detected.

01 Oct 2024·Retina

GENETIC ETIOLOGY AND CLINICAL FEATURES OF ACHROMATOPSIA IN JAPAN

Article

Author: Ota, Junya ; Inooka, Taiga ; Iwata, Takeshi ; Kondo, Mineo ; Suga, Akiko ; Hayashi, Takaaki ; Yoshitake, Kazutoshi ; Kominami, Taro ; Goto, Kensuke ; Ueno, Shinji ; Tsunoda, Kazushige ; Kuniyoshi, Kazuki ; Nishiguchi, Koji M. ; Mizobuchi, Kei ; Kondo, Hiroyuki

Purpose:To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM.Methods:The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study.Results:Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C.Conclusion:The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.

10 Sep 2024·Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

[Genetic analysis of a Chinese pedigree affected with Achromatopsia due to variants of CNGA3 gene and a literature review].

Review

Author: Liu, Yingwen ; Xie, Min ; Yan, Lulu ; Li, Haibo ; Zhang, Yuxin

OBJECTIVETo explore the molecular basis for a Chinese pedigree affected with Achromatopsia (ACHM).METHODSA pedigree with ACHM which was admitted to the Women and Children's Hospital of Ningbo University on April 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. Related literature was reviewed, and clinical and genetic features of Chinese patients with ACHM due to variants of CNGA3 gene were summarized.RESULTSWES revealed that the proband and his younger brother had both harbored compound heterozygous variants of the CNGA3 gene, namely c.1190G>T (p.Gly397Val) and c.2013del (p.Gly672ValfsTer69), which were respectively inherited from their mother and father. The c.1190G>T was a known pathogenic variant, whilst the c.2013del was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2013del variant was predicted to be likely pathogenic (PM2_Supporting+PVS1_Moderate+PM3+PP4). Literature review has identified 41 CNGA3 gene variants among 43 patients from 38 pedigrees, most of which were missense variants and had located in exon 8. Most patients were males, with nystagmus, photophobia, amblyopia and other symptoms during infancy/childhood as the main clinical manifestations, and there was a lack of genotype-phenotype correlation.CONCLUSIONThe c.1190G>T (p.Gly397Val) and c.2013del (p.Gly672ValfsTer69) variants of the GNGA3 gene probably underlay the ACHM in the proband. Discovery of the c.2013del variant has enriched the mutational spectrum of the GNGA3 gene and provided a basis for genetic counseling and reproduction guidance for this pedigree.

News (Medical) associated with Achromatopsia 1

09 May 2023

·www.prnewswire.com

Significant Positive Shift in the Cell and Gene Therapies in Rare Disorders Market with 35.8% CAGR During the Study Period (2019-2032) Expected by Analysts at DelveInsight

The dynamics of the cell and gene therapies market in rare disorders are anticipated to change as companies across the globe are thoroughly working toward developing new therapeutic options to treat a wide array of indications. LAS VEGAS, May 9, 2023 /PRNewswire/ -- DelveInsight's Cell and Gene Therapies in Rare Disorders Market Insights report includes a comprehensive understanding of current treatment practices, emerging cell and gene therapies for various rare disorders, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Key Takeaways from the Cell and Gene Therapies in Rare Disorders Market Report As per DelveInsight analysis, the cell and gene therapies in rare disorders market size in the 7MM was approximately USD 1.5 billion in 2022. According to the assessment done by DelveInsight, the estimated total prevalent cases of selected indications for cell and gene therapies in rare disorders in the 7MM were approximately 900K in 2022. Leading companies developing novel cell and gene therapies for various rare disorders, such as Hemophilia A, Hemophilia B, Fabry disease, Retinitis Pigmentosa, Amyotrophic Lateral Sclerosis, Duchenne Muscular Dystrophy, and others include Roche, Freeline Therapeutics, Spark Therapeutics, Astellas Gene Therapies, Actus Therapeutics, GenSight Biologics, Coave Therapeutics, Johnson & Johnson, MeiraGTx, Applied Genetic Technologies Corporation, GenSight Biologics, Nanoscope Therapeutics, 4D Molecular Therapeutics, Ocugen, jCyte, ReNeuron, REGENXBIO, Amicus Therapeutics, Pfizer, Sarepta Therapeutics, Capricor Therapeutics, Nippon Shinyaku, Brainstorm Cell Therapeutics, CRISPR Therapeutics, Vertex Pharmaceuticals, Editas Medicine, Sangamo Therapeutics, Krystal Biotech, Abeona Therapeutics, Castle Creek Biosciences, Holostem Terapie Avanzate S.r.l., RHEACELL, Ishin Pharma, Anterogen, Ultragenyx Pharmaceutical, and others. The promising cell and gene therapies for various rare disorders in the pipeline include Giroctocogene fitelparvovec, Dirloctocogene samoparvovec, Fidanacogene elaparvovec, Verbrinacogene setparvovec (FLT-180a), FLT190, Isaralgagene civaparvovec (ST-920), 4D-310, SPK-3006, AT845, ACTUS-101, LUMEVOQ (lenadogene nolparvovec), CTx-PDE6b, Botaretigene sparoparvovec, ATGC-501 (laruparetigene zosaparvovec), GS030, MCO-010 (sonpiretigene isteparvovec), 4D-125, OCU400, jCell, RGX-121, AT-GTX-502 (scAAV9.P546.CLN3), PF-06939926, SRP-9001, CAP-1002, NurOwn (MSC-NTF cells), Exagamglogene autotemcel, EDIT-301, BIVV003, VYJUVEK (beremagene geperpavec), EB-101, D-Fi (dabocemagene autoficel), RV-LAMB3-transduced epidermal stem cells, Allogeneic ABCB5-positive Stem Cells, ISN001, ALLO-ASC-SHEET, DTX301, UX111 (ABO-102), DTX401 (AAV8G6PC), and others. In July 2022, the Institute for Clinical and Economic Review (ICER) released a final evidence report assessing the comparative clinical effectiveness and value of ZYNTEGLO (betibeglogene autotemcel) for treating beta-thalassemia. In May 2022, Orchard Therapeutics reached an agreement with Gesetzliche Krankenversicherung Spitzenverband (GKV-SV), which will result in reimbursed access to LIBMELDY (atidarsagene autotemcel) for all metachromatic leukodystrophy (MLD) patients in Germany who fall within the scope of the European marketing authorization. Discover which therapies are expected to grab the major cell and gene therapies in rare disorders market share @ Cell and Gene Therapies in Rare Disorders Market Report Cell and Gene Therapies in Rare Disorders Overview Cell and gene therapies use genes and cells to treat disease. A gene is a unit of DNA containing genetic information passed down from generation to generation. The genome comprises all genes; genes may contain information on observable features such as height or eye color. Many genes contain instructions for RNA or protein molecules that are not visible from the outside but serve crucial tasks in the body's cells. Cells are the building blocks of plants and animals (including humans); they are small functional units that work together to generate organs and tissues. Cell and gene therapy technology is quickly evolving for many different diseases. However, cell and gene treatments are still experimental drugs, and much more study is required before many of these therapies are available to patients worldwide. Cell and Gene Therapies in Rare Disorders Epidemiology Segmentation DelveInsight estimates that there were approximately 900K prevalent cases of selected indications for cell and gene therapies in rare disorders in the 7MM in 2022. As per our analysis, the highest prevalent cases from the selected indications for cell and gene therapies in rare disorders were for Retinitis Pigmentosa in the United States, whereas the least cases were reported for Hunter Syndrome in 2022. The cell and gene therapies in rare disorders market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total Prevalent Cases of Shortlisted Indications for Cell and Gene Therapies in Rare Disorders Total Indication Eligible-wise Cases for Cell and Gene Therapies in Rare Disorders Indication-wise Treated Cases of Cell and Gene Therapies Cell and Gene Therapies in Rare Disorders Market Insights Numerous cell and gene therapies for rare diseases are currently approved in the 7MM, including retinitis pigmentosa ( LUXTURNA), beta-thalassemia ( ZYNTEGLO), epidermolysis bullosa ( JACE), limbal stem cell deficiency ( OCURAL), and many others. As per Delveinsight analysis, the total cell and gene therapies in rare disorders market size was around USD 1.5 billion in 2022. According to predictions, the United States will have the largest cell and gene therapies in rare disorders market. ZOLGENSMA produced the highest revenue of roughly USD 1 billion among the 7MM in 2022, while ROCTAVIAN is predicted to take the highest market share by 2032. ROCTAVIAN has received conditional approval in Europe for the treatment of severe hemophilia A. In addition to this approval, BioMarin Pharmaceutical is working to approve the drug in the United States, with a PDUFA target action date of June 30, 2023. Hemophilia A is predicted to produce the most revenue among the selected indications by 2032, owing to the precedence of existing high treatment cost and expected high cost for emerging therapies along with significant residual unmet need. Gene treatments for Hemophilia A are estimated to earn around USD 6 billion in sales revenue by 2032 in the 7MM. The field of cell and gene therapies for rare indications is expected to rapidly expand in the coming years, as an increasing number of companies submit investigational new drug applications for these treatments each year, along with rising regulatory approval in the United States and Europe. In terms of manufacturing aspects of cell and gene therapies, there will be more competition for contract manufacturing businesses and pharmaceutical/biotechnology firms. The competition for contract manufacturing organization's production capacity will intensify as more companies enter the cell and gene therapy market, possibly driving up manufacturing costs. To ensure pharmaceutical/biotechnology firms can compete or obtain an advantage over competitors, companies may need to invest in manufacturing technologies or acquire companies with manufacturing expertise. To know more about cell and gene therapies in rare disorders treatment guidelines, visit @ Cell and Gene Therapy Insights Emerging Cell and Gene Therapies for Hemophilia A and Key Companies Giroctocogene fitelparvovec: Pfizer/Sangamo Therapeutics Dirloctocogene samoparvovec: Roche Emerging Cell and Gene Therapies for Hemophilia B and Key Companies Fidanacogene elaparvovec: Pfizer/Spark Therapeutics Verbrinacogene setparvovec (FLT-180a): Freeline Therapeutics Emerging Cell and Gene Therapies for Fabry Disease and Key Companies FLT190: Freeline Therapeutics Isaralgagene civaparvovec (ST-920): Sangamo Therapeutics 4D-310: 4D Molecular Therapeutics Emerging Cell and Gene Therapies for Pompe Disease and Key Companies SPK-3006: Spark Therapeutics AT845: Astellas Gene Therapies ACTUS-101: Actus Therapeutics Emerging Cell and Gene Therapies for Leber Hereditary Optic Neuropathy and Key Companies LUMEVOQ (lenadogene nolparvovec): GenSight Biologics Emerging Cell and Gene Therapies for Retinitis Pigmentosa and Key Companies CTx-PDE6b: Coave Therapeutics Botaretigene sparoparvovec: Johnson & Johnson/ MeiraGTx ATGC-501 (laruparetigene zosaparvovec): Applied Genetic Technologies Corporation GS030: GenSight Biologics MCO-010 (sonpiretigene isteparvovec): Nanoscope Therapeutics 4D-125: 4D Molecular Therapeutics OCU400: Ocugen jCell: jCyte Emerging Cell and Gene Therapies for Hunter Syndrome and Key Companies RGX-121: REGENXBIO Emerging Cell and Gene Therapies for Batten Disease and Key Companies AT-GTX-502 (scAAV9.P546.CLN3): Amicus Therapeutics Emerging Cell and Gene Therapies for Duchenne Muscular Dystrophy (DMD) and Key Companies PF-06939926: Pfizer SRP-9001: Sarepta Therapeutics CAP-1002: Capricor Therapeutics/Nippon Shinyaku Emerging Cell and Gene Therapies for Amyotrophic Lateral Sclerosis (ALS) and Key Companies NurOwn (MSC-NTF cells): Brainstorm Cell Therapeutics Emerging Cell and Gene Therapies for Beta Thalassemia and Sickle Cell Anemia and Key Companies Exagamglogene autotemcel: CRISPR Therapeutics/Vertex Pharmaceuticals EDIT-301: Editas Medicine BIVV003: Sangamo Therapeutics Emerging Cell and Gene Therapies for Dystrophic Epidermolysis Bullosa and Key Companies VYJUVEK (beremagene geperpavec): Krystal Biotech EB-101: Abeona Therapeutics D-Fi (dabocemagene autoficel): Castle Creek Biosciences RV-LAMB3-transduced epidermal stem cells: Holostem Terapie Avanzate S.r.l. Allogeneic ABCB5-positive Stem Cells: RHEACELL ISN001: Ishin Pharma ALLO-ASC-SHEET: Anterogen Emerging Cell and Gene Therapies for Ornithine Transcarbamylase Deficiency and Key Companies DTX301: Ultragenyx Pharmaceutical Emerging Cell and Gene Therapies for Sanfilippo Syndrome Type A and Key Companies UX111 (ABO-102): Ultragenyx Pharmaceutical Emerging Cell and Gene Therapies for Glycogen Storage Disease Type IA and Key Companies DTX401 (AAV8G6PC): Ultragenyx Pharmaceutical Learn more about the FDA-approved cell and gene therapies for rare disorders @ Approved Cell and Gene Therapies in Rare Disorders Treatment Cell and Gene Therapies in Rare Disorders Market Dynamics The cell and gene therapies in rare disorders market is predicted to grow positively due to an increase in the approval of a growing number of gene therapies and their ease of adoption following approval, the ability to treat a wide range of conditions, an increase in the number of cases, an expected one-time dosing approach, and curative treatment options. The approval of LIBMELDY, SKYSONA, HOLOCLAR, UPSTAZA, ROCTAVIAN, and other medicines has successfully created regulatory channels for the development of further cell and gene therapies. Companies around the world are working hard to develop new cell and gene therapies options to treat a wide range of indications, such as hemophilia A and B, lysosomal storage disorder (Fabry, Pompe Disease, Danon Disease, MPS I, MPS II, MPS III), neurological disorders (Batten, Parkinson), musculoskeletal disorders (DMD, myotubular myopathy), eye diseases (achromatopsia, limbal stem cell deficiency, retinitis pigmentosa, retinoschisis, age-related macular degeneration, Leber's hereditary optic neuropathy), and other indications such as diabetic macular edema, inborn metabolism disorder (Wilson's disease, Phenylketonuria, OTC deficiency/urea cycle disorders), dystrophic epidermolysis bullosa, gangliosidosis, and xerostomia. Many diseases' treatment landscapes have drastically evolved in the last few years. Companies are now developing cell and gene therapies that will play an important role in the future, particularly in the treatment of rare genetic disorders. The process of defining ideal candidates for given gene therapy and cell therapy will have to wait for the enrolment and long-term follow-up of a sufficient number of study subjects to provide satisfactory clarity regarding its safety and efficacy. In conclusion, the future of cell and gene therapy looks optimistic. Several clinical trials have yielded favorable results in terms of safety and efficacy. The findings of these studies motivate additional research into many indications, and the current scenario predicts a positive shift in the cell and gene therapies in rare disorders market for the forecast period. However, several factors may impede the growth of cell and gene therapies in rare disorders market in the coming years. Despite advances since the enactment of the Orphan Drug Act, people in the United States with rare diseases continue to face challenges to diagnosis, care, and treatment. Moreover, in Europe, a possible crisis with gene treatments for rare diseases is developing, and few companies have withdrawn the drug after failing to get reimbursement in the EU. Scope of the Cell and Gene Therapies in Rare Disorders Market Report Therapeutic Assessment: Cell and Gene Therapies in Rare Disorders current marketed and emerging therapies Cell and Gene Therapies in Rare Disorders Market Dynamics: Conjoint Analysis of Emerging Cell and Gene Therapies in Rare Disorders Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's Views, Analyst's Views, Cell and Gene Therapies in Rare Disorders Market Access and Reimbursement Discover more about cell and gene therapies for rare disorders in development @ Cell and Gene Therapy Clinical Trials Table of Contents Related Reports Gene and Cell Therapies in Rare Disorder Epidemiology Forecast Gene and Cell Therapies in Rare Disorder Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted gene and cell therapies in rare disorder epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Cell And Gene Therapy For Multiple Myeloma Market Cell And Gene Therapy For Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key cell and gene therapy for multiple myeloma companies, including Pfizer, MorphoSys, Biokine Therapeutics, Arcellx, Rapa Therapeutics, among others. Gene Therapy For Ocular Rare Disease Pipeline Gene Therapy For Ocular Rare Disease Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key gene therapy for ocular rare disease companies, including Roche Holding, Novartis, Ocugen, among others. Adeno-Associated Virus Vectors in Gene Therapy Market Adeno-Associated Virus Vectors in Gene Therapy Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key adeno-associated virus vectors in gene therapy companies, including Pfizer, CSL Behring, Spark Therapeutics, Freeline Therapeutics, RegenxBio, Amicus Therapeutics, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Gene TherapyOrphan DrugDrug Approval

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis