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Thursday, March 20, 2008

Pivotal proteins may point to eye cure



By Abram Katz
Register Science Editor

Using medical breakthroughs at Yale, a New Haven biotechnology company is poised to start working on a novel potential treatment for age-related macular degeneration, the leading cause of irreversible vision loss in the U.S.
Optherion Inc., is already synthesizing pivotal proteins in its Maritime Center headquarters.
And if research, development and a $37 million business plan work out, the pre-clinical protein synthesis will be upgraded to an industrial scale.
Scheer & Co. Inc., another New Haven firm, is helping arrange investments in Optherion. Amanda Hayward, vice president of Scheer, and Colin J. Foster, president and chief executive officer of Optherion, sounded an optimistic note Wednesday at a meeting of Connecticut United for Research Excellence Inc. held at Yale.
Hayward said there is no treatment for “dry” age related macular degeneration, and only modestly effective treatments for “wet” AMD.
About 15 million to 20 million people in the U.S. have AMD. The condition starts with deposits of “drusen” (tiny yellow or white accumulations of extracellular material) in the retina, a layer of neurons and blood vessels at the back of the eyeball that send visual signals to the brain.
The drusen form on the inside of the eye, where they have no effect. However, they can cover the macula, a small, delicate patch of the retina that allows detailed vision. Once in the macular the drusen lodge between the retina’s blood supply and its sensory rods and cones. As the disease progresses the drusen spread and become soft, separating retinal nerves from their life-sustaining blood.
The condition worsens until the blood vessels start to leak, and new blood vessels grow over the retina. This is “wet” macular degeneration and can rapidly cause blindness.
The composition of drusen was not known until Dr. Gregory Hageman at Yale and Josephine Hoh at Rockefeller University made a breakthrough in 2005, Hayward said.
Hageman and colleagues found that drusen were composed of proteins that occur in the immune system’s complement cascade.
The complement cascade is normally triggered to destroy alien organisms, while preventing “bystander” damage to surrounding tissue.
With AMD, the complement cascade was apparently acting abnormally, creating an inflammatory disease, Hayward said. The complement cascade is controlled by Complement Factor H, or CFH.
Hageman and colleagues realized macular degeneration is rooted in malformed CFH that cannot inhibit itself. Optherion’s strategy is to balance mutated CFH with normal, protective CFH assembled in a laboratory.
The regular CFH could balance, or supplant the mutated version, stopping formation of drusen, Foster said.
During the course of research, scientists discovered that mutated CFH also is responsible for a rare kidney disorder.
In fact, correcting malfunctioning CFH could prove helpful in a range of immune and inflammatory diseases, including Alzheimer’s disease, multiple sclerosis, asthma, stroke and heart attack.
Foster said pre-clinical tests have shown recombinant CFH is not toxic to test animals. Several large pharmaceutical companies have shown interest in the research, Hayward said.
In the nearer future, the same biotechnology and genetic testing could be used to assess the risk of AMD.
“Biology is swimming in our favor,” Foster cautioned, “but the bogeyman is always around the corner.”
Abram Katz can be reached at akatz@nhregister.com.

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