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Biotech / Medical : Incyte (INCY) -- Ignore unavailable to you. Want to Upgrade?

To: nigel bates who wrote (1466)	5/26/2000 9:35:00 AM
From: Biomaven	Read Replies (2) \| Respond to of 3202

There's a front page WSJ article today about J&J's finding the gene for H-3. Here's the part relevant to INCY: In 1996, Dr. Lovenberg was recruited by Johnson & Johnson to lead its effort to find new drug targets among the family of G-protein-coupled receptors. His primary resource was an ever-growing database of tiny gene fragments developed by Incyte Pharmaceuticals, to which J&J and about 20 other drug companies are subscribers. Meanwhile, using other libraries containing sequences of known receptor genes, the institute's researchers were looking for matches among the Incyte fragments. They piled up hundreds of hits, which were dispatched automatically as strands of letters and numbers to a Johnson & Johnson database dubbed Gold Nuggets. That's where Dr. Lovenberg, scrolling down the list on his computer screen in mid-1998, spotted a small sequence of letters characteristic of the protein family he was looking for. Using chemical techniques that promote rapid replication of genes, Dr. Lovenberg's team made enough copies of that Incyte sequence to screen it against a template of 50 different human tissues to find out where in the body the gene associated with the fragment was active. The fewer the tissue types in which it is found, the better the potential target, because that implies a very specific function that might be "treated" without causing unwanted reactions elsewhere in the body. In this case, the gene appeared to be most active in a section of the brain called the thalamus -- posing the tantalizing prospect that it was a gene that controlled a neurotransmitter; such signal agents for central-nervous-system functions have proven to be good drug targets. That led researchers to construct another library, this one of DNA associated with the human thalamus. Using the fragment much like a bit of genetic Velcro, they managed to pluck out the complete sequence of a gene for a G-protein-coupled receptor. From there, about three months after Dr. Lovenberg's initial hunch, the researchers quickly closed in on its function. They inserted the gene into human tissue cells, coaxing the cells to produce an excess of the gene's associated protein. Then, they exposed the cells to a flurry of neurotransmitters -- such as acetylcholine, norepinephrine, dopamine and histamine. "It only responded to one thing -- histamine," recalls Dr. Lovenberg. "That was the end of the story." Well, not exactly. Without having isolated the gene itself, several drug companies had previously developed compounds that blocked the H-3 protein in lab experiments but proved ineffective or toxic when tested in people, and so went nowhere. Those compounds still were available as research tools, and when Johnson & Johnson scientists tested them against the receptor protein, all of them locked onto it. "It was crystal clear within a matter of days," says Dr. Lovenberg. Undisclosed Hopes Now, with target in hand, Johnson & Johnson is betting it will succeed in developing an effective H-3-based medicine. The company, which is based in New Brunswick, N.J., won't say what disease it hopes its promising drug candidate will treat but says it identified the compound with the help of a new robotic technology called high-throughput screening. In less than a month, they tested a library of more than 200,000 compounds -- a task that Dr. Lovenberg calculates would have taken 25 researchers using conventional techniques a year to complete. All told, by mining the human genome for a specific receptor family and applying advanced drug-hunting technology to the task, the company went from picking a target to developing a potential drug in just 18 months, a process that typically takes five years or more. "This is a best-case scenario," says Dr. Lovenberg. Not every DNA snippet reveals its secrets so quickly or so readily leads to a potential drug. Moreover, there isn't yet any technology to automate the complex and labor-intensive process of conducting drug trials in humans. It will take several years before a Johnson & Johnson drug targeting the H-3 gene reaches the market -- if one does at all. Peter