In the News

As reported by The Hartford Courant, August 17, 2007.

A Visionary Study At UConn

By William Hathaway

In their search for a cancer cure, a few scientists have managed to shed light on new ways to help the near blind see again.

Researchers have found ways to reduce the tangle of blood vessels that not only feed cancer tumors but contribute to the loss of vision linked to macular degeneration and diabetic retinopathy, two of the most common causes of blindness in the United States. In some cases, new drugs that combat the growth of blood vessels, a process called angiogenesis, have actually improved vision in some people with a common form of macular degeneration.

In a study published Thursday by the Journal of Clinical Investigation, UConn Health Center researcher Timothy Hla described another potential way to stunt the growth of unruly blood vessels that can lead to blindness.

Hla's lab showed that in mice the protein S1P, or sphinogosine 1 phosphate, was crucial to the growth of blood vessels from the retina into the eye, a hallmark of diabetic retinopathy.

Hla proposes that blocking S1P may halt angiogenesis in the human eye as well. If he is right, science will have another potential drug in a growing arsenal that may be able to help patients preserve sight, or even restore it.

"These drugs represent a huge paradigm shift for all of ophthalmology," said Dr. Elizabeth Simmons, an ophthalmologist at the UConn Health Center. "Prior to these medications, treatment of [macular degeneration] was just slowing down the disease process and hoping to preserve vision. Today, some patients are actually improving, and that never happened before."

"They have introduced an element of hope, and in some cases visual improvement, which had not been achieved before," agreed Dr. Hanna Coleman, an ophthalmologist at New York-Presbyterian Hospital and a liaison to the National Eye Institute, part of the National Institutes of Health.

The drugs on the market work by blocking VEGF, a protein known to stimulate the growth of blood vessels in development and wound repair. However, cancer also hijacks VEGF and other angiogenesis proteins to feed tumors as they spread to other parts of the body. Those proteins have become a prime target for cancer researchers in the past 20 years.

The growth of blood vessels in mice used in cancer research could be clearly tracked in the whites of the animals' eyes. Scientists noticed that the blood vessels disappeared in mice treated with agents that blocked VEGF.

"A blood vessel is a blood vessel," whether in the eye or any other part of the body, Hla noted.

The observation led to the development and approval of the drugs Macugen in 2003 and three years later Lucentis. Lucentis was shown to actually improve the vision of about 30 percent of people with macular degeneration, in which blood vessels form behind the retina at the rear of the eye. Some smaller scale studies have also shown that such drugs may benefit people with proliferative diabetic retinopathy, characterized by blood vessel growth inside the eye.

The drugs do have drawbacks, Simmons said. It is still unknown how often people should receive injections, and they are very expensive.

Each dose of Lucentis, made by Genentech, costs more than $2,000, Simmons said. Clinical trials for Lucentis called for patients to undergo monthly injections for two years.

Some doctors are now prescribing the cancer drug Avastin, which is very similar to Lucentis and also made by Genentech but costs much less. The National Eye Institute is conducting a trial comparing the efficacy of Avastin and Lucentis in treating macular degeneration.

Coleman and Simmons say studies such as Hla's are crucial to developing new treatments to complement the new medications on the market. Even with the advances, they note, only a minority of patients improve.

Ironically, the eventual treatment model for eye disease may mimic those for cancer, Coleman said.

"The eventual approach may be similar to that of cancer, a multi-drug approach," Coleman said. "I don't think we will have a one-drug miracle. We are likely going to need more than one for a cure."