Researchers in the US have identified a chemical which dissolves the protein clumps of cataracts, which could potentially form the basis of an eye drop treatment.
Cataract occurs when the crystallin proteins of the lens lose their ordered structure and form clumps. In a healthy lens, crystallins maintain their ordered transparent structure, while being able to flex and stretch, due to chaperon proteins which sit in between them. But as the eye ages, or in inherited conditions, the crystallin proteins become misfolded, forming persistent amyloid clumps which make the lens cloudy.
While cataract operations are a common day procedure in the UK, the World Health Organization lists the condition as a ‘priority eye disease’ which is responsible for an estimated 51% of blindness worldwide.
In the search for new treatments, a team of researchers from the University of California, San Francisco (UCSF), University of Michigan and Washington University, screened a stock of 2450 compounds, whittling the number down to a handful of potentials.
One of the compounds, named ‘compound 29,’ was found to prevent crystallins from forming clumps in laboratory tests, and even dissolved clumps of protein which had already formed.
When delivered via eye drops, compound 29 was shown to reduce the cloudiness of the lenses in mice predisposed to cataracts. Similar results were seen when the compound was tested on human cataractous lens tissue, removed during surgery.
“We are starting to understand the mechanism in detail,” said Dr Jason Gestwicki, associate professor of pharmaceutical chemistry at UCSF and senior author on the study, adding; “We know where compound 29 binds, and we are beginning to know exactly what it’s doing.”
Compound 29 is one of a class of molecules called sterols, important organic molecules which play a wide role of biological functions, such as precursors to steroid hormones. The team found that the compound fits between subunits of the protein, stabilising it.
Earlier this year, researchers in China and the US identified another sterol, lanosterol, as having potential to be the first in a new class of drug to treat cataracts after successful animal experiments in dogs and rabbits.
A postdoctoral fellow in Dr Gestwicki’s lab, and lead author of the latest study, Leah Makely, is founder and chief scientific officer of ViewPoint Therapeutics, which is actively developing compound 29 for human use.
The findings offer raise the possibility of using sterols, such as compound 29, in neurological conditions involving protein clumps, such as Alzheimer’s or Parkinson’s disease.
Dr Gestwicki said: “By studying cataracts we’ve been able to benchmark our technologies and to show by proof-of-concept that these technologies could be used in nervous system diseases, to lead us all the way from the first idea to a drug we can test in clinical trials.”
The research is published in the journal Science.