Summary
Dr. Peter Campochiaro, professor of ophthalmology and neuroscience at Johns Hopkins, discusses NAC's potential for preserving cone vision in retinitis pigmentosa (RP). His research showed that after rod photoreceptors degenerate in RP, oxygen levels rise dramatically, causing oxidative damage to remaining cone cells. NAC, as a powerful antioxidant, was found to reduce cone cell death in animal models. A preliminary trial of 30 RP patients showed oral NAC reaches the eye and produced small but significant improvements in visual acuity over six months. This led to the $20 million NEI-funded NAC Attack trial enrolling 438 patients across 33+ sites to test whether long-term NAC treatment can slow RP progression.
Key Points
- Oxidative damage from excess oxygen is a major contributor to cone cell death in retinitis pigmentosa
- NAC reduced cone cell death in multiple animal models of RP
- A 30-patient trial showed oral NAC reaches the eye and produced small but significant improvements in cone function over 6 months
- The NAC Attack trial is a $20 million NEI-funded study enrolling 438 patients at 33+ sites worldwide
- The trial tests whether 45 months of NAC treatment can slow RP progression by measuring remaining cones
- NAC was first approved as a drug in 1963 for acetaminophen toxicity and has a well-established safety profile
- NACA (N-acetylcysteine amide) is a modified form that penetrates cell membranes better but has less safety data
Key Moments
Oxidative stress from excess oxygen kills cone cells in retinitis pigmentosa
Dr. Campochiaro explains how when rod photoreceptors degenerate in RP, oxygen levels in the retina rise dramatically. Since rods make up 95% of outer retina cells, their loss leads to excess oxygen that overwhelms the endogenous antioxidant defense system and damages remaining cone cells.
"After the rods degenerate, the levels of oxygen in the retina go way up. And so putting those two things together, that in RP, after rods degenerate, and the way that that works is that the mutations that cause RP predominantly affect the rods. And the rods constitute 95% of the cells in the outer retina."
Oral NAC reaches the eye and improved cone function in a 30-patient trial
In a preliminary trial of 30 RP patients over 6 months, Dr. Campochiaro found that oral NAC reaches the eye and produced small but significant improvements in best corrected visual acuity and macular sensitivity, suggesting NAC helps cone cells when given orally.
"in the eye. So we found that with giving oral NAC, it does get into the eye. And then, as you mentioned, there were small but significant changes in measures of cone cell function, such as best corrected visual acuity, just a gradual small improvement over the six months, and also mean macular sensitivity with micropyramidry. So that suggests that it's doing at least something"
NAC Attack is a $20M trial enrolling 438 patients to test long-term NAC for RP
The NAC Attack study is a multi-center, placebo-controlled, double-masked trial funded by the National Eye Institute for approximately $20 million. It enrolls 438 patients with early-stage RP across 33 sites worldwide, monitoring cone parameters every 9 months for 45 months.
"The projected enrollment is 438 patients. And so we have to have a lot of sites. And so we have 33 sites throughout the United States."
