UCSF

Study identifies eye-drop-soluble compound that could treat cataracts

Cataracts are the leading cause of blindness worldwide, the leading cause of vision loss in the United States, and cases are increasing with an aging population. Currently the condition can be treated with surgery—an expensive intervention that leaves most patients blinded in developing countries untreated.

A cataract occurs when the lens of the eye loses its transparency. This happens because protein molecules called crystallins—the main components of the fiber cells that form the lens—are damaged such that they misfold into insoluble forms that aggregate into clumps called amyloids. In healthy eyes, such clumping is resisted by chaperone proteins, which aid the proper folding of other proteins, such as crystallins, into their functional shapes.

A recently published paper in the journal Science, co-senior-authored by UCSF School of Pharmacy faculty member Jason Gestwicki, PhD, reports on the identification of a class of molecules that bind to crystallins and reverse their harmful aggregation in laboratory tests. The molecules act as pharmacological chaperones that stabilize the soluble forms of crystallins to reduce amyloid formation. One such molecule, dubbed compound 29, was also soluble enough to be delivered via eye drops.

A team of scientists, including Gestwicki and his co-authors at University of Michigan and Washington University in St. Louis, tested compound 29 in eye drops applied to mice with genetic mutations predisposing them to cataracts (a model of the familial form of the condition in humans). They found that the newly discovered chemical partially restored transparency to the mouse lenses, according to an eye exam commonly used to measure cataracts.

The researchers also tested compound 29 in eye drops applied to mice that had developed age-related cataracts. In addition, they applied the drops to human lens tissue that was removed during cataract surgery. In those cases, the compound partially restored crystallin protein solubility.

Gestwicki cautions that the research findings are not a direct measure of restored or improved vision. Clinical trials in humans are needed to determine the value of compound 29 as a cataract treatment.

Indeed, in order to do just that, the compound has been licensed by Gestwicki from the University of Michigan, where his lab was formerly based. The chemical is now in active development for human use by ViewPoint Therapeutics, a company formed through the incubator program of the California Institute for Quantitative Biosciences (QB3) at UCSF and founded by Leah Makley, PhD, co-lead author of the Science article.

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About the School: The UCSF School of Pharmacy is a premier graduate-level academic organization dedicated to improving health through precise therapeutics. It succeeds through innovative research, by educating PharmD health professional and PhD science students, and by caring for the therapeutics needs of patients while exploring innovative new models of patient care. The School was founded in 1872 as the first pharmacy school in the American West. It is an integral part of UC San Francisco, a leading university dedicated to promoting health worldwide.