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Guilford Pharmaceuticals Reports Success in Study With New Neuroprotective Approach
September 16, 1997 11:45 AM EDT
Results of Animal Experiments With PARP Inhibitor Being Presented Today at The Fifth International Meeting on the Biology of Nitric Oxide
BALTIMORE, Sept. 16 /PRNewswire/ -- Guilford Pharmaceuticals Inc. (Nasdaq: GLFD) today announced that it has demonstrated positive results in an animal model of stroke using a prototype compound, GPI-6000, which acts through a novel mechanism of action, based on inhibition of PARP (poly-ADP- ribosyl-polymerase). The results are being presented today at The Fifth International Meeting on the Biology of Nitric Oxide in Kyoto, Japan.
PARP is an enzyme found in the nucleus of cells. Its normal function is believed to involve repair of cellular DNA. Stroke and other conditions which result in diminished bloodflow cause DNA damage, which in turn activates PARP. Over-stimulation of PARP during ischemic conditions causes a depletion of energy levels in the cell, which result in brain cell death.
The study presented today describes the results of experiments conducted with a prototype small molecule PARP inhibitor, GPI-6000, in a rat model of stroke. In these experiments the middle cerebral artery of rats was occluded, to induce focal ischemia and mimic the damage caused by a stroke. Administration of GPI-6000 two hours before and two hours after the experimentally induced ischemia produced a significant neuroprotective effect and reduction in the volume of brain damage compared with control animals.
"This study demonstrated for the first time that administration of a PARP inhibitor leads to a significant reduction of injury in this rat model of stroke. Our results suggest that PARP activation plays an important role in the brain damage that occurs in stroke due to energy depletions. Thus, PARP inhibition may offer a novel therapeutic approach for developing neuroprotective agents for the treatment of stroke. Further evidence supporting this new discovery is expected to be published in a major scientific journal before the end of the year," commented Dr. Peter Suzdak, Vice President of Research at Guilford.
"PARP inhibition is one key element in our multi-pronged neuroprotective research program. Our goal is to target critical points in the complex cascade of events which results in brain cell death during stroke. There appear to be multiple complex biological consequences of stroke, and potentially a number of different ways to intervene to try to reduce the damage. However, it appears that PARP may be one of the last important steps in the process. Similarly, one of our other programs is targeting inhibition of pre-synaptic glutamate release, which is believed to be one of the first steps in the cascade. Both of these programs are part of our commitment to develop novel agents for the treatment of stroke and other ischemic disorders," said Dr. Craig Smith, President & C.E.O. of Guilford.
Guilford Pharmaceuticals Inc. is a biopharmaceutical company engaged in the development of polymer-based therapeutics for cancer, and novel products for the diagnosis and treatment of neurological diseases, including Parkinson's disease, Alzheimer's disease, stroke, severe head trauma, spinal cord injuries, multiple sclerosis, peripheral neuropathies, and cocaine addiction.
This press release contains forward-looking statements that involve risk and uncertainties, including those described in the section entitled "Risk Factors" from the Company's registration statement on Form S-3, declared effective April 7, 1997, that could cause the Company's actual results and experience to differ materially from anticipated results and expectations expressed in these forward-looking statements. In particular, the pre- clinical results discussed above are based on a limited number of animals and animal models, and obtained with a prototype compound intended to help establish proof of principle, but not intended to be a product candidate, and there can be no assurance that the Company will be able to successfully develop one or more of its compounds into a safe and effective FDA-cleared drug. SOURCE Guilford Pharmaceuticals Inc. |
