Drug designed to help alcoholics might be the key to treating progressive blindness

Disulfiram is the oldest drug out there to treat alcoholism, but new research might be giving it a second life in a very different field.

The drug is designed to inhibit the enzymes necessary to metabolize alcohol, which is what makes drinking while taking it so unpleasant. But disulfiram also decreases the body’s ability to make retinoic acid, which is linked to vision loss. After administering the drug to nearly blind mice, a team of researchers at University of California (UC), Berkeley found that the mice were much more able to detect images on a computer screen compared to mice that weren't given disulfiram.

This work could have serious implications for anyone with retinitis pigmentosa (RP), a genetic disorder that slowly breaks down cells in the retina, causing progressive vision loss over time. RP is the No. 1 inherited cause of blindness, affecting roughly one in every 4,000 people in the U.S. The research team, led by Richard Kramer, Ph.D., of UC Berkeley and Michael Goard, Ph.D., of UC Santa Barbara, is planning a clinical trial to test disulfiram for patients with RP.

"There may be a long window of opportunity in which suppressing retinoic acid with drugs like disulfiram could substantially improve low vision and make a real difference in people’s quality of life," Kramer said in a statement.

The researchers conducted two experiments to see how disulfiram would affect mice with significantly diminished eyesight. In the first, they trained young mice who still had good vision to respond to a specific image on a screen, and, after their eyesight had decreased a month later, they showed them the same image. Only the mice who had been treated with disulfiram were still able to recognize and respond to the image.

The second experiment was designed to see how each group of mice responded to more complex images, which involved showing them a movie clip on a loop while tracking their brain activity. Again, the treated mice responded much more, with stronger and more consistent activity that showed the mice were reacting to specific frames and not just light in general, suggesting improved vision overall.

“Treated mice really see better than mice without the drugs. These particular mice could barely detect images at all at this late stage of degeneration. I think that that's quite dramatic," Kramer said.

Retinoic acid is created when rods and cones, the cells in the retina responsible for detecting color and light, begin to die off. Once the acid is produced, it starts to interfere with the cells that send visual information to the brain, which is responsible for some of the eyesight loss associated with RP. If approved as a treatment, disulfiram could stop the cells from producing retinoic acid, decreasing RP's effect for those whose retinal cells have already been majorly diminished.

There have been other developments around treatment for RP and related eye diseases in the past, with research in 2020 on a potential gene therapy to prevent cell degradation and in 2018 a gene transfer treatment to activate retinal stem cells. Both, however, are focused around slowing or reversing the progression of the disease rather than treating its effects.

“If a vision impaired human were given disulfiram, and their vision got better, even a little bit, that would be a great outcome in itself,” said Kramer. “But it would also strongly implicate the retinoic acid pathway in vision loss. And that would be an important proof of concept that could drive new drug development and a whole new strategy for helping to improve vision."