CLEVELAND—There’s only one U.S. Food and Drug Administration-approved therapy for an inherited retinal disease, and dozens of retinitis pigmentosa (RP) genes for which no therapy is available.
With a new three-year, $1.5 million grant from the Foundation Fighting Blindness, Shigemi Matsuyama, an associate professor of ophthalmology and visual sciences at the Case Western Reserve University School of Medicine, will test a possible breakthrough drug that can be taken by mouth—one that may address many RP disease manifestations, regardless of the underlying genetic mutation.
“We believe it can serve as the basis of an oral medicine to prevent blindness in RP patients, regardless of the underlying gene mutations,” Matsuyama said.
The disease…and promising science
RP causes blindness when cells in the retina that respond to light—called photoreceptors—die.
In a previous foundation-funded drug discovery program from 2017-20, Matsuyama and his research team developed a series of novel orally-active cell-death inhibitors—known as Cytoprotective Small Compounds (CPSCs)—which work by blocking the activation of Bax, a protein that contributes to cell death. Their lead compound prevented retinal cell death and vision loss in four mouse models of inherited retinal disease.
The proposed studies, which include toxicology evaluation and drug-formulation testing—for both oral drugs and eye drops—are aimed at advancing the technology to U.S. Food and Drug Administration (FDA)-regulated clinical trials.
“Our primary objective is bringing an CPSC-based therapeutic to RP patients who are suffering from the fear of blindness,” Matsuyama said.
Bax-induced cell death is also a major cause of various neurodegenerative conditions, including glaucoma, ischemia-reperfusion injury, amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.
“Therefore,” he said, “there is significant potential to expand the application of our Bax-inhibiting therapeutic for additional uses.”
“The Foundation Fighting Blindness is proud to support Dr. Shigemi Matsuyama’s research,” said Chad Jackson, senior director of preclinical translational research at the foundation. “Through this award, we continue our commitment to advancing scientific discoveries that have the potential to realize tangible solutions for those affected by inherited retinal diseases.”
About the Foundation Fighting Blindness
The foundation is focused on treating and curing blindness caused by the spectrum of blinding retinal diseases including: RP, macular degeneration and Usher syndrome.
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