The Hindu: Health » Medicine & Research October 21, 2010 Lasker Award winner finds way to fight blindness D. BALASUBRAMANIAN Share · Comment · print · T+ SAVING SIGHT: Patients with wet age-related macular degeneration are now treated with Lucentis injections. Photo: S.R. Raghunathan The HinduSAVING SIGHT: Patients with wet age-related macular degeneration are now treated with Lucentis injections. Photo: S.R. Raghunathan
Early October is the season for the announcement of the Nobel Prizes, thought to be the highest recognition in the world for outstanding achievement. The Nobel Prize for Medicine went to Dr. Edwards, the IVF pioneer. At about the same time also comes the announcement of the Lasker Awards, equally prestigious awards given for outstanding biomedical research. And it is generally believed that if one gets the Lasker, the Nobel usually follows, and the other way around as well. Interestingly however, Dr. Edwards got his Lasker in 2001, and had to wait for the Nobel until now. While the Nobel is named after Alfred Nobel, the Swedish scientist, the Laskers are named after the philanthropic couple Albert and Mary Woodward Lasker of the US, and have been given for the past 60 years. This year's Lasker goes to four scientists, each of whom gets $250,000. These are David Weatherall of Oxford, UK in recognition of his decades of work in understanding and treating the inherited blood disease thalassemia; Douglas Coleman retired from Jackson Labs, Maine, USA) and Jeffrey Friedman (Rockefeller University, New York), who share the prize for their work on the hormone called leptin which controls our appetite (and shortfall in which is associated with obesity); and the fourth one is Napoleone Ferrara (of biotech firm Genentech in San Francisco, USA, who gets the Lasker for his 25 years of work on angiogenesis, the process by which the body grows new blood vessels. It is Ferrara's work that we shall discuss in this article. A nice summary is found in the Lasker website, from where I have taken generous portions here. Blood is a fluid that nourishes the body. It is a rich mixture of proteins oxygen and other small molecules that make cells function, grow and make more of themselves (proliferate). This can be both good (which is what we want normally) and bad (when we do not want certain cells to grow-as in cancer). Also, there are certain tissues where we do not want blood vessels criss-crossing and impede transparency (as in the eye). Already, over 100 years ago, researchers found that blood vessels proliferate before and during the growth of cancer cells into tumour. This led Dr. Judah Folkman of Harvard (who passed away recently) to suggest 40 years ago that if we restrict blood vessel growth or angiogenesis to tumours, we could starve the tumour cells to death and win over cancer. This provided the impetus to look for molecules or factors that help the growth of blood vessels, or angiogenesis promotion. What then are these growth factors? By the early 1980s, two candidates appeared on the scene, namely fibroblast growth factors a and b (aFGF, bFGF). Fibroblasts are cells that act as strings that tie up together to make connective tissues. This was an exciting discovery, except for one thing. These growth factors are stuck inside cells and do not come out; how then can they help neighbouring cells grow, migrate and form blood vessels? A growth factor needs to get out and trigger the process. So, back to the lab again to look for diffusible growth factors. It is here that Ferrara's sustained work becomes valuable. As a post-doctoral fellow at the University of California, San Francisco, he studied the pituitary gland cells which help in the development of blood vessels. While growing the pituitary gland cells in a flask, he decided to look not just within the cells but in the medium or broth in which they grow, the idea being lo look for factors that have come out of the cells and can diffuse out to help angiogenesis. When this “rich” medium was added to blood vessels, they proliferated. He then went ahead and isolated various components of the medium and found the molecule that fit the bill. It was named vascular endothelial growth factor or VEGF. It is VEGF that helps grow the cells that line blood vessels, the so called vascular endothelial cells. If VEGF is to induce endothelial cells to proliferate, the latter should have the “lock” on their outer surface into which VEGF must fit as the “key” and do its job. So, are there such “locks” or VEGF receptors on cell surfaces? Ferrara's next step was to look for isolate and study these putative receptors. He found them. Then again, if one can find a way to block these locks or receptors such that VEGF cannot fit in there, would such decoy molecules not stop blood vessel proliferation and stop tumour growth? Yes indeed, one can raise antibody molecules – proteins that fit the receptors like a glove and block VEGF from getting there. Such an antibody was his next discovery. Thanks to this work, Genentech was able to produce and market this antibody called Lucentis, a drug that helps control angiogenesis in the retina of the eye. Patients with a form of blinding disease called wet age-related macular degeneration (wet AMD) are now treated with Lucentis injections to help preserve their sights. Genentech also developed a similar antibody called Avastin to fight cancer, using the same idea of blocking the ‘lock' on the surface of cancer cells, rather than retinal cells. This too is out in the market and used as an anticancer drug. [email protected] To unsubscribe send a message to [email protected] with the subject unsubscribe. To change your subscription to digest mode or make any other changes, please visit the list home page at http://accessindia.org.in/mailman/listinfo/accessindia_accessindia.org.in
