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Inotek Pharmaceuticals Announces Publication of Animal Data from,Study of PARP Inhibition as Potential Preventative of Brain Injury,Following Stroke

BEVERLY, Mass.--(BUSINESS WIRE)--Apr 10, 2007 - Inotek Pharmaceuticals Corporation announced today the publication in the journal Stroke of preclinical animal data showing that the administration of a poly(ADP-Ribose) polymerase (PARP) inhibitor has a large protective effect on the survival of certain brain cells following a stroke. PARP is a nuclear enzyme that directs the repair of damaged DNA via the activation and recruitment of DNA repair enzymes and has potential applications for the treatment of cardiovascular conditions, oncology, and inflammatory disorders.

In the study, researchers from Professor Raymond Swanson's team at the University of California, San Francisco examined the use of a PARP inhibitor, PJ34, in a rat model of cerebral ischemia-reperfusion. Ischemia is a restriction in blood supply to a tissue, whereas reperfusion injury refers to tissue damage caused when blood supply is returned to that tissue. Rats were subjected to 10 minutes of cerebral ischemia and then treated with PJ34 or placebo (saline) for seven days beginning eight hours after the onset of reperfusion.

Researchers measured the activation of brain macrophages, known as microglial cells, at several time-points between 0 and 14 days following ischemia. Microglial activation is an important component of the brain's inflammatory response and precedes neuronal death. Rats treated with PJ34 exhibited near-complete suppression of microglial response after 5 days, and similar responses were also observed at other timepoints. At 7 days post-ischemia, neuronal survival was evaluated. PJ-34 reduced neuronal death in the CA1 hippocampus region by 84% in treated rats relative to control rats.

"We now have support for PARP inhibition as a potential method of suppressing brain inflammation and preventing injury following ischemia-reperfusion," said Andrew Salzman, M.D., President and Chief Executive Officer of Inotek. "These
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