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Israeli Medical Researchers Are Architects Of A New Drug

October 29, 2009
In pre-clinical studies, a new drug, L803-MTS, shows promise as a treatment for a number of central nervous system (CNS) diseases like Alzheimer’s, Parkinson’s, Huntington’s and diabetes. L803-MTS is based on the physical structure of the GSK3 protein, a factor in insulin resistance and Type 2 diabetes. Working with chemists, biotechnologists and 3-D modelists, Professor Hagit Eldar-Finkelman of Tel Aviv University’s Sackler School of Medicine and her colleagues built—like engineers constructing a building—a drug that locks onto the GSK3 protein, rendering it harmless and unable to wreak havoc inside the body. Since Professor Eldar-Finkelman linked GSK3 to insulin resistance in diabetes more than 10 years ago, a race has been on among drug manufacturers to find a drug that can potentially turn off the harmful effects of GSK3. But rather than build on existing drugs, Eldar-Finkelman and her colleagues worked from the ground up. "I decided to take a completely different approach from all the big drug companies rushing to find the ultimate drug," says Eldar-Finkelman. "I designed my own." Pre-clinical results have been positive, and the new drug does not exhibit dangerous toxic side effects, a problem with existing formulations. While L803-MTS cannot reverse the onset of a CNS disease once it has started, Eldar-Finkelman believes it can slow down the devastating effects of CNS diseases, like impaired memory and depression, or insulin-resistance. "One important thing to note is that our drug acts differently than other compounds," she says. "Most GSK3 inhibitors are developed on the basis of ATP competitors. Ours are substrate competitors, meaning that they bind to a different site at the surface of the protein. This strategy is completely different and yields a better and safer compound." Additional pharmacological and toxicological tests are now underway. Eldar-Finkelman  believes L803-MTS will be a lead compound for treating CNS disorders "because it was based on rational drug design. We started from scratch and thought through the design of a specific compound that would be safe and effective. Our aim is to slow the progression of CNS diseases, but the new drug might also be used as a preventative therapy."