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Vertex Pharmaceuticals/Yale Research Team Uses Gene Knockout Mice To Establish Role Of Caspase-9 In Neuronal Cell Death Pathway

Cambridge, MA, August 7, 1998 -- A team of scientists from Vertex Pharmaceuticals, Yale University School of Medicine, Howard Hughes Medical Institute (HHMI) at Yale University, and Tokyo Metropolitan Institute of Medical Science (TMI) reported results with a gene knockout mouse that establishes a key role for the enzyme Caspase-9 in a specific biochemical pathway that results in neuronal cell death. These findings, published in the August 7, 1998 issue of Cell, suggest that blocking Caspase-9 may be a viable strategy for treating a variety of acute and chronic age-related neurological diseases, including Alzheimer's disease, Parkinson's disease and stroke.

Caspases comprise a family of enzymes that are being evaluated for their role in a number of diseases, based on their involvement in biochemical pathways of inflammation and of apoptosis (also known as programmed cell death or cell suicide). Apoptosis is an essential component of numerous biological processes, including tissue remodeling, immune system regulation and embryonic development. Abnormal activation of apoptosis, however, is implicated in the development and progression of a number of different human diseases, and links between specific caspases and specific diseases are beginning to be established. The publication of the Cell paper is the first report describing the in vivo function of Caspase-9, and suggests apparent tissue-selective activity among the eleven reported human caspases.

"When mitochondria -- the energy factory of cells -- are damaged, Caspase-9 is activated leading to cell death," said Dr. Richard A Flavell, an HHMI Investigator and an author of the study. "In cells lacking Caspase-9, this damage did not give rise to cell death."

"Our results also indicate that Caspase-9 is activated early and is essential for apoptosis in neuronal cells, and that deletion of Caspase-9 does not interfere with embryonic development of other non-neuronal tissues," said Dr. Keisuke Kuida, St
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Contact: Michael Partridge
partridge@vpharm.com
(617) 577-6108
Vertex Pharmaceuticals
7-Aug-1998


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