Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration

May 23, 2006

BOSTON, MA - Harvard Medical School announced today that is has signed a multimillion-dollar license agreement with Merck & Co., Inc. to develop potential therapies for macular degeneration, an eye disease that affects older people and can lead to blindness. The agreement provides Merck, through an affiliate, with licenses to specific molecules that could ultimately slow the production of toxic by-products that form in the eye and that have been implicated in some forms of age-related macular degeneration (AMD) and Stargardt Disease, a juvenile form of blindness. The agreement also establishes a research collaboration between Merck and Robert Rando, PhD, HMS Professor of Biological Chemistry and Molecular Pharmacology and provides Merck, through an affiliate, with exclusive rights to Dr. Rando's intellectual property in this area.

"This agreement is an example of the kind of strategic partnerships that we like to build with an industrial partner to bring fundamental research forward as a potential new therapy," said Isaac T. Kohlberg, head of Harvard's technology development office. "By combining the licensing rights and the expertise behind the original findings, and partnering with a leading company such as Merck, we can advance this research into clinical development and application much faster than would otherwise be possible."

Under the terms of the agreement, Harvard will receive a $3 million up-front payment, significant milestone fees and downstream royalties on any marketed products that result from this agreement.

"We are delighted to partner with Harvard on the development of this potential breakthrough technology to treat dry AMD," said Dr. Robert Gould, Vice President Worldwide Licensing and External Research at Merck. "Merck has a long history of research and marketing in ophthalmology including the introduction of the first glaucoma therapy in 1958. This agreement demonstrates Merck's continuing commitment to treat major diseases of the eye. Fundamental research at major research universities such as Harvard is having a more immediate impact on therapeutic approaches, and this new dynamic requires both world class science and strong partnerships between technology transfer organizations, academic scientists and industry," Dr. Gould added.

Eight million people in the U.S. have the dry form of AMD, a condition for which neither definitive causes nor cures are known.

Studies on vision and AMD by Dr. Rando have recently culminated in the development of small molecule antagonists of the visual cycle that may protect against dry AMD and Stargardt disease.

Dr. Rando's approach is to prevent toxic substances called lipofuscins from forming in the eye. "Lipofuscin accumulation appears to be a major risk factor for macular degeneration, including the age-related type," said Dr. Rando. Toxic constituents of lipofuscin are generated as byproducts of the visual cycle, a complex chemical pathway that is required for the maintenance of the light gathering components of the eye called retinal photoreceptors. The macula is the portion of the retina that is responsible for color and high acuity vision.

When light hits the retina, which is packed with photoreceptor cells, a complex chemical process occurs that stimulates the optic nerve. During this process, essential components of the photoreceptors, called chromophores, are photochemically modified as a consequence of light absorption. Retinal photoreceptors and associated retinal pigment epithelial cells repair these altered chromophores, but the photochemically modified chromophores can also chemically react with other molecules in the retina, especially lipids, to form toxic by-products. The most common by-products of the vision cycle comprise the lipofuscins, which are very stable toxic substances, and not readily eliminated from the eye.

The lipofuscins can be compared to cholesterol because monitoring and lowering these toxic molecules could do for macular degeneration what cholesterol measurements and cholesterol-lowering drugs, such as the statin class, have done for cardiovascular disease. In some cases of macular degeneration called geographic atrophy, holes appear in the macula that are surrounded by clumps of lipofuscin. "One of the worrisome issues with the lipofuscins is that they are insoluble and form aggregates akin to plaques, suggested Dr. Rando. In addition, he noted the lipofuscins and their readily formed oxidation products are highly retinotoxic for a variety of reasons, which includes their propensity to react with DNA and other macromolecules.

One way to stop the formation of lipofuscin is to put a brake on the vision cycle. In a 2005 issue of Biochemistry, Dr. Rando and his collaborators reported finding key elements in the visual cycle pathway and designed a group of novel small molecule antagonists for some of them. Their approach is illustrated by studies on the functional and mechanistic importance of a protein that is almost exclusively found in the retinal pigment epithelium, and is essential for the vision cycle. In two additional and previous publications in 2004, one in the Proceedings of the National Academy of Sciences and another in Cell, Dr. Rando and his team found evidence to suggest that this protein is involved in the slow step of the cycle, making it a potential drug target. As anticipated, small molecule antagonists of this target both selectively inhibit this protein's function and slow the visual cycle. As further described in the January 24, 2006 issue of the journal Biochemistry, Dr. Rando, members of his research team, and collaborators at Columbia University, selected small molecule antagonists that they had previously synthesized and showed that they can also stop production of the retinotoxic lipofuscins. In mice that are genetically predisposed to forming excessive amounts of lipofuscin, administration of the inhibitors completely blocked formation of the A2E lipofuscins, the most common components of lipofuscin found in the eye.

"Our own work focuses on basic, mechanistic chemical approaches to understanding the biology of vision. Now that it is time to translate this work into the clinic, it is important to hand it over to experts at using applied chemical and biological approaches," Dr. Rando said. "These approaches are far more effectively executed in the pharmaceutical industry than in academia and that is why we are partnering with Merck."
Harvard Medical School has more than 7,000 full-time faculty working in eight academic departments based at the School's Boston quadrangle or in one of 47 academic departments at 18 Harvard teaching hospitals and research institutes. Those Harvard hospitals and research institutions include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, the CBR Institute for Biomedical Research, Children's Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Massachusetts Mental Health Center, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Harvard Medical School

Related Macular Degeneration Articles from Brightsurf:

Levodopa may improve vision in patients with macular degeneration
Investigators have determined that treating patients with an advanced form of age-related macular degeneration (AMD) with levodopa, a safe and readily available drug commonly used to treat Parkinson's disease, stabilized and improved their vision.

Combating drug resistance in age-related macular degeneration
An international team of researchers led by Baylor College of Medicine and Houston Methodist has discovered a strategy that can potentially address a major challenge to the current treatment for age-related macular degeneration,

Study finds unexpected suspect in age-related macular degeneration
Scientists have identified an unexpected player in the immune reaction gone awry that causes vision loss in patients with age-related macular degeneration (AMD), according to a new study published today in eLife.

Potential way to halt blinding macular degeneration identified
It would be the first treatment for dry age-related macular degeneration and could significantly improve treatment for wet AMD.

Heating techniques could improve treatment of macular degeneration
Age-related macular degeneration is the primary cause of central vision loss and results in the center of the visual field being blurred or fully blacked out.

Eye's vulnerability to macular degeneration revealed
Scientists have found significant differences in the shape and biology of the same type of cell taken from different parts of the retina, according to a study in eLife.

Hallucinations associated with brain hyperactivity in people with macular degeneration
New research from The University of Queensland has shown for the first time that visual hallucinations in people with macular degeneration are associated with abnormally heightened activity in the visual cortex of the brain.

Eating leafy greens could help prevent macular degeneration
A new study has shown that eating vegetable nitrates, found mainly in green leafy vegetables and beetroot, could help reduce your risk of developing early-stage age-related macular degeneration (AMD).

An orange a day keeps macular degeneration away: 15-year study
A new study has shown that people who regularly eat oranges are less likely to develop macular degeneration than people who do not eat oranges.

Macular degeneration linked to aging immune cells
Studying mice and cells from patients, vision researchers at Washington University School of Medicine in St.

Read More: Macular Degeneration News and Macular Degeneration Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.