Collaborating on Sight Research

Surprising genetic finding raises hope for treating retinal disease that causes blindness

Scientists thought they knew the IMPDH genes and their proteins. After 30 years of study, the two genes were known to be vital in the synthesis of an important DNA building block, with a potential role in the treatment of cancer and immune disease.

Today, an international, multidisciplinary group is trying to understand something else: how variations of IMPDH1 slowly rob people of their sight – 4,000 adults in the United States alone.

Biochemists, geneticists and microbiologists from academia and the private sector gathered in Houston in July to compare notes on the gene and its role in one version of retinitis pigmentosa, which causes slow deterioration of the retina and ultimately, blindness.

“At the top of everyone’s priority list coming out of that meeting is determining why these mutations cause retinal damage,” said the meeting organizer, Stephen Daiger, Ph.D., professor of epidemiology in the Human Genetics Center at The University of Texas School of Public Health at Houston.

The result of the collaboration could be something unprecedented: a cure for a form of retinitis pigmentosa. Daiger, who is the Thomas Stull Matney, Ph.D., Endowed Professor in Environmental and Genetic Sciences and a faculty member in the UT Graduate School of Biomedical Sciences at Houston, believes it will take the varied perspectives of geneticists, pharmacologists and biochemists to advance that cause.

Daiger’s lab made the surprising initial genetic connection two years ago. Research Associate Sara Bowne, Ph.D., authored a paper tying variation in IMPDH1 to a version of retinitis pigmentosa known as RP10. Both IMPDH1 and IMPH2 play a role in creating guanine, one of the building blocks of DNA.

Daiger’s team was delighted that their findings pointed to a well-known gene and that researchers elsewhere already made drugs that suppressed both proteins. He began to connect with new collaborators outside his field, as well as longtime genetics colleagues.

At the July meeting, scientists came from the University of Pennsylvania, University of North Carolina, Brandeis University, the Center for Drug Design at the University of Minnesota, Baylor College of Medicine, and Trinity College and University College, both in Dublin, Ireland.

Jugnu Jain, Ph.D., an executive at Vertex Pharmaceuticals of Cambridge, Mass., also attended. To treat cancer and immune disease, Vertex develops pharmaceuticals that inhibit production of IMPDH enzymes by the genes. “We inhibit the enzyme activity. In this case, are increased levels of the enzyme needed? It’s a new area,” Jain said.

New collaborations are under way. Daiger’s group sent genetic samples to Liz Hedstrom, Ph.D., associate professor of biochemistry at Brandeis, who in turn shared some new lab techniques.

“I think this meeting will have catalyzed a lot of research,” Daiger said. “But if you really want to know how successful this meeting was, you’ll have to wait a few years and see the results.”

The meeting was supported by grants from the National Eye Institute, the Hermann Eye Fund and
Alfred W. Lasher III.

— By Scott Merville, Public Affairs