Prolexys Pharmaceuticals, Inc. and Collaborators Publish Data Identifying the Protein Interaction Network in Huntington's Disease

SALT LAKE CITY, May 11 /PRNewswire/ -- Prolexys Pharmaceuticals announced today the publication of the first extensive description of the protein interaction network of the huntingtin (Htt) protein. Huntington's Disease (HD) is a fatal neurodegenerative condition caused by a large stretch of amino acid glutamine (polyglutamine tract) in the huntingtin (Htt) protein. Huntington's disease affects as many as 200,000 people in the U.S. The illness typically onsets in middle age and is characterized by dementia, loss of movement control and eventually death by heart failure, infection or choking -- usually within 10 to 15 years. The mutated polyglutamine form of Htt is improperly folded and therefore likely plays an important role in the elaboration of the disease phenotype because of the protein interactions that are unique to the mutated Htt.

The results, published in the April 2007 issue of PLoS Genetics, are the result of a collaborative effort. The Prolexys Project Leader for this study was Dr. Robert Hughes, now an assistant professor at the Buck Institute for Age Research in Novato, California. Other collaborators included the scientists from the Baylor College of Medicine, Houston, and Fred Hutchinson Cancer Research Center in Seattle, Washington. These studies demonstrate that high-throughput screening for protein interactions combined with genetic validation provides an opportunity to understand the biological basis of the diseases associated with polyglutamine toxicity.

Protein-Protein interactions in normal and polyglutamine-Htt were elucidated by employing a high-throughput version of the yeast 2-hybrid assay (HyNet(TM)) developed at Prolexys. The second process, affinity pull-down followed by mass spectrometry (HySpec(TM)), employed purified huntingtin protein as bait to identify proteins that bind specifically to either normal or polyglutamine form of huntingtin protein. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method (HyNet(TM)) and 130 with the pull downs (HySpec(TM)). Of the 234 hits, 60 genes were tested in a Drosophila fruit fly model to determine if they had anything to do with Huntington's disease. Validation experiments in fruit fly resulted in the identification of 17 loss-of-function suppressors, or genes which upon knock down cause an improvement in the disease phenotype.

The 17 genes identified in this study therefore represent potential targets for therapeutic intervention in HD. "The results of this study demonstrate the power of using the protein interaction discovery technologies in conjunction with the functional validation experiments to understand the disease biology and to identify potential therapeutic intervention points," said Dr. Sudhir Sahasrabudhe, Chief Scientific Officer of Prolexys Pharmaceuticals.

About Prolexys Pharmaceuticals, Inc.

Prolexys Pharmaceuticals, Inc. is a privately held biopharmaceutical company focused on discovering small molecule drugs that act at novel therapeutic targets. The Company's ability to identify and validate novel targets is driven by its technological leadership in the field of proteomics and the application of proteomics technologies to its own, and its partners, drug discovery programs. Prolexys' internal drug discovery programs focus on cancer indications where the Company has identified novel therapeutic targets and small molecule compounds with promising anti-tumor activity.

Prolexys Pharmaceuticals, Inc.

CONTACT: Dr. Sudhir Sahasrabudhe, Chief Scientific Officer of ProlexysPharmaceuticals, Inc., +1-801-303-1714, or cell, +1-801-891-7880,sudhir@prolexys.com