Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial
Peter A. Campochiaro, … , Mandeep S. Singh, Xiangrong Kong
Peter A. Campochiaro, … , Mandeep S. Singh, Xiangrong Kong
Published December 5, 2019
Citation Information: J Clin Invest. 2020;130(3):1527-1541. https://doi.org/10.1172/JCI132990.
View: Text | PDF
Clinical Research and Public Health Neuroscience Ophthalmology Article has an altmetric score of 9

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

  • Text
  • PDF
Abstract

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 < 0.001), 0.5 (95% CI: 0.3–0.7, P < 0.001), and 0.2 (95% CI: 0.02–0.4, P = 0.03) letters/month in cohorts 1, 2, and 3, respectively. There was no significant improvement in mean sensitivity over time in cohorts 1 and 2, but there was in cohort 3 (0.15 dB/month, 95% CI: 0.04–0.26). There was no significant change in mean EZ width in any cohort.CONCLUSION Oral NAC is safe and well tolerated in patients with moderately advanced RP and may improve suboptimally functioning macular cones. A randomized, placebo-controlled trial is needed to determine if oral NAC can provide long-term stabilization and/or improvement in visual function in patients with RP.TRIAL REGISTRATION NCT03063021.FUNDING Mr. and Mrs. Robert Wallace, Mr. and Mrs. Jonathan Wallace, Rami and Eitan Armon, Marc Sumerlin, Cassandra Hanley, and Nacuity Pharmaceuticals, Inc.

Authors

Peter A. Campochiaro, Mustafa Iftikhar, Gulnar Hafiz, Anam Akhlaq, Grace Tsai, Dagmar Wehling, Lili Lu, G. Michael Wall, Mandeep S. Singh, Xiangrong Kong

×

Figure 6

Heatmaps and fundus images from microperimetry testing during treatment and posttreatment observation in a patient from cohort 1 and a patient from cohort 2.

Options: View larger image (or click on image) Download as PowerPoint
Heatmaps and fundus images from microperimetry testing during treatment ...
The heatmaps generated by the Macular Integrity Assessment Instrument software (A–D and I–L) and fundus images showing the sensitivity value at each retinal location (E–H and M–P) obtained pretreatment, during treatment at weeks 12 and 24, and after treatment at week 36 are shown for 1 eye for a cohort 1 patient (1-09) and 1 eye for a cohort 2 patient (2-05). Two pretreatment tests were obtained and the one with the highest mean sensitivity is shown. In heatmaps, the arrows point to regions where the retinal sensitivity improved after the onset of treatment. A change from an arrow to an arrowhead indicates improvement had occurred, and any subsequent decline is noted by a change from arrowhead to arrow. The loci circled in yellow on the pretreatment fundus images (E and M) show loci at which sensitivity increased equal to or more than 6 dB after the onset of treatment. On subsequent fundus images, green circles indicate that sensitivity at that location was increased equal to or more than 6 dB from pretreatment and a change back to yellow indicates a decline below the 6 dB threshold. In both of these eyes, there was a large improvement in sensitivity during treatment that was mostly sustained in A–H and partially sustained in I–P 3 months after treatment ended.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 9 X users
Referenced in 1 patents
On 1 Facebook pages
97 readers on Mendeley
See more details