New Drug May Reverse Retinopathy: How It Works

| May 11, 2007

Let’s start from the beginning. First, you’ve got the endothelium.  What’s that, you ask? Well, endo means “internal” and thelium means “cellular layer.” The endothelium, therefore, is the layer of cells that lines the heart, blood vessels, and certain other cavities in the body.

Next vocabulary word: VEGF.  It stands for vascular endothelial growth factor. In other words, it’s a factor that causes the growth of vascular (blood vessel) endothelium. VEGF also promotes angiogenesis, which is the growth, or genesis, of new blood vessels (angio means vessel in Greek). Some studies indicate that VEGF goes up when blood glucose levels are high.

VEGF, reasonably enough, plays a role in diabetic proliferative retinopathy. That’s when abnormally fragile new blood vessels grow, or proliferate, on the retina and then leak and cause scar tissue. Over-active VEGF is also implicated in wet macular degeneration, in which new blood vessels grow below the retina and into the macula (center of the retina). These fragile new vessels burst easily, leaking blood and fluid under the macula and causing scarring. VEGF is about 40,000 times more potent at stimulating leakage and swelling than histamine, which causes the swollen eyes related to allergies.

It was cancer researchers who first realized that by blocking VEGF, they could inhibit angiogenesis around a tumor and thereby perhaps starve the tumor into submission.  By 2006, the FDA had approved an anti-VEGF drug, Avastin (bevacizumab), for the treatment of coleorectal and lung cancers. Subsequently, an adventurous ophthalmologist discovered that very small doses of Avastin injected into the eye were effective against wet macular degeneration. Meanwhile, Genentech, the company that produces Avastin, re-engineered its initial raw material (mouse anti-VEGF antibody) to create a new treatment for age-related wet macular degeneration. The result is Lucentis (ranibizumab), which was FDA approved for wet macular degeneration in June 2006.

Once Lucentis was approved for wet macular degeneration, some ophthalmologists, including Dr. Mark Michels, decided to try it off-label as a treatment for diabetic macular edema (retina swelling caused by leakage within the macula) associated with diabetic retinopathy. Dr. Michels has used it successfully on twelve people who didn’t respond to traditional treatment with laser therapy or steroid injections. After injections of Lucentis, their vision doubled on average, and their retinal swelling was reduced by an average of 25 percent.

Dr. Michels notes, “It’s not for everybody, but for those without options, it was very exciting to see substantial improvement with this technique. I can’t tell you how excited we are for these twelve people.  One patient was a mechanic who loves to read science fiction, and now he can read his favorite books again.”

Genentech, in partnership with the JDRF, is planning to begin clinical trials this summer to formally test Lucentis as a treatment for diabetic retinopathy.

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Categories: Blood Glucose, Diabetes, Diabetes, Eye Care (Retinopathy), Reversing Complications, Type 1 Issues

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