Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial

BACKGROUND In retinitis pigmentosa (RP), rod photoreceptors degenerate from 1 of many mutations, after which cones are compromised by oxidative stress. N-acetylcysteine (NAC) reduces oxidative damage and increases cone function/survival in RP models. We tested the safety, tolerability, and visual function effects of oral NAC in RP patients.METHODS Subjects (n = 10 per cohort) received 600 mg (cohort 1), 1200 mg (cohort 2), or 1800 mg (cohort 3) NAC bid for 12 weeks and then tid for 12 weeks. Best-corrected visual acuity (BCVA), macular sensitivity, ellipsoid zone (EZ) width, and aqueous NAC were measured. Linear mixed-effects models were used to estimate the rates of changes during the treatment period.RESULTS There were 9 drug-related gastrointestinal adverse events that resolved spontaneously or with dose reduction (maximum tolerated dose 1800 mg bid). During the 24-week treatment period, mean BCVA significantly improved at 0.4 (95% CI: 0.2–0.6, P
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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In this study, we identified two unrelated Japanese patients with clinical diagnoses of BBS associated with compound heterozygousSCLT1 mutation. Patient 1 was a 10-year-old girl, and patient 2 was a 22-year-old man. Both the patients showed severe renal dysfunction in childhood, RP, mild intellectual disability, short stature, and truncal obesity, without oral aberrations and polydactyly. Patient 2 also had hypogonadism. We identified two missense variants inSCLT1, c.[1218G  >  A] and [1631A >  G], in both the patients by next-generation sequencing. Subsequent cDNA analysis revealed that c...
Source: CEN Case Reports - Category: Urology & Nephrology Source Type: research
Purpose of review Gene therapy offers, for the first time, the possibility to cure diseases such as retinitis pigmentosa. The positive outcomes that led to the U.S. Food and Drug Administration (FDA) approval of Luxturna to treat Leber congenital amaurosis caused by RPE65 mutations created an optimistic atmosphere in the research, clinical and patient community. Despite this first success, we must understand that this is not a ‘one treatment for all’. This review aims to explain the basic concepts of gene therapy and how they translate in different approaches that are utilized in ongoing clinical trials here ...
Source: Current Opinion in Ophthalmology - Category: Opthalmology Tags: RETINAL, VITREOUS AND MACULAR DISORDERS: Edited by Brandon G. Busbee and John W. Kitchens Source Type: research
Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photoreceptor cells against both light-induced and inherited retinal degeneration. Upon light damage, photoreceptor cells upregulate Kit ligand (KITL) and activate KIT signaling, which in turn induces nuclear accumulation of the transcription factor NRF2 and stimulates the expression of the antioxidant geneHmox1. Conversely, a viableKit m...
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research
Publication date: April 2020Source: Stem Cell Research, Volume 44Author(s): Yalan Zhou, Chengcheng Ding, Shutao Xia, Yutong Jing, Shengru Mao, Jian Liu, Juan Chen, Hon fai Chan, Shibo Tang, Jiansu Chen
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Conclusions: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness-blindness association. PMID: 32214787 [PubMed - in process]
Source: Molecular Vision - Category: Molecular Biology Tags: Mol Vis Source Type: research
Conclusions: CEP290 mutations are associated with a variety of overlapping clinical phenotypes, some of which will become better understood as more patients with these conditions survive to reproductive age. Similarly, increased understanding of the molecular mechanisms that underlie differences in phenotype may provide avenues to consider in future therapies. PMID: 32208788 [PubMed - as supplied by publisher]
Source: Ophthalmic Genetics - Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
Condition:   Retinitis Pigmentosa Interventions:   Biological: Umbilical Cord Mesenchymal Stem Cell (UC-MSC);   Biological: Conditioned Medium (CM) Sponsor:   PT. Prodia Stem Cell Indonesia Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Authors: Rohrschneider K, Bolz HJ Abstract The Bardet-Biedl syndrome (BBS) is a rare inherited ciliopathy, which is accompanied by retinal disease, i.e. rod-cone dystrophy (retinitis pigmentosa, RP) and other symptoms, especially truncal obesity, polydactyly, renal abnormalities as well as reduced intelligence or learning difficulties. 25 BBS genes are currently known, and these are responsible for the structure and function of primary cilia. Because ciliary integrity is crucial for numerous pathways of developmental signaling, their dysfunction may cause multisystemic disorders - like BBS. Physicians benefit great...
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
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