Date: Nov 01, 2011 Author: Deborah Erickson Source: Irish Media (
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Extract taken from Start UP Magazine
An article by Deborah Erickson in the most recent issue of Start Up Magazine outlines the work of ONL Therapeutics LLC who are developing an experimental drug to preserve sight in people with detached retinas and other retinal disorders. The start-up aims to leverage understanding about FAS, a cell-based receptor that is a key cause of cell death in photoreceptors. ONL's small peptide is designed to block the FAS receptor on cells of the eye, to keep the natural ligand from binding and keep the cells alive
It is well known that certain kinds of drugs given soon after heart attacks and strokes can help slow the death of heart and brain cells injured by trauma, and thereby lead to better outcomes for patients. ONL Therapeutics LLC, a start-up spun out of the University of Michigan Kellogg Eye Institute believes the same principle may allow an experimental drug to preserve sight in people with detached retinas. Potentially, other common retinal disorders that lead to blindness, such as the initial dry form of age-related macular degeneration and the more serious, advanced wet form, might also be helped by the treatment.
The start-up aims to leverage understanding about an important molecular pathway that leads to the death of photoreceptors, the light-processing eye cells vital to vision. David Zacks, an associate professor of ophthalmology at the university, explains that animal studies in his lab show that a cell-based receptor called FAS is a key cause of cell death in photoreceptors. The discovery is not a total surprise; this receptor, naturally bound by a protein called FAS ligand, is known to stimulate cell death, alias "apoptosis," in many systems. Indeed, the acronym FAS stands for fragment apoptosis stimulator.
The company aim to develop a small peptide to block the FAS receptor on cells of the eye ultimately keeping the cells alive. He says he identified the drug candidate, now dubbed ONL-101, through an online literature search; it had originally been tested in humans at the University of Pittsburgh, with the hope that it could help protect liver cells after acute hepatic injury. Zacks figured the trial failed because the peptide was degraded in the bloodstream and reasoned that injecting the peptide directly into the eye might yield better results, because the eye is something of a privileged environment.
In untreated animal models where the retina is kept detached for two months, about half of the photoreceptors die, he says. By contrast, in animals given just one injection of the peptide, only about 10 to 15% of the cells die. "That's a promising ratio for a potential therapeutic," Zacks declares. "If you can preserve 85 to 90% of the photoreceptors in people with a retinal disorder, instead of 50%, that is likely to let them keep a lot more of their vision."
ONL Therapeutics has filed patents covering use of the peptide in the eye, and is now proceeding with all the basic development tasks such as product formulation and pharmacologic and toxicology testing that the FDA requires before granting permission for an Investigational New Drug trial. Zacks says his company will first test the compound as an adjunct to surgery for repair of detached retinas, to see if it can improve outcomes.
If human trials of the peptide as an adjunct to retinal re-attachment surgery, expected to begin within two to three years, ultimately do show a benefit, Zacks anticipates the molecule could also be developed as a treatment for other kinds of retinal disorders in which progressive vision loss occurs because of cell loss. "We think our compound can be adjunctive to therapies that exist now or that may come to exist."