Targeting two with PTP1B

CSHL-Glaxo collaboration looks to combat diabetes and obesity by regulating enzymatic activity of phosphatase PTP1B

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COLD SPRING HARBOR, N.Y.—Diabetes affected 366 million people worldwide in 2011, a figure that is expected to increase to 552 million by 2030, according to the International Diabetes Federation. In the U.S. alone, the annual health cost of obesity-related conditions is nearly $200 billion. Cold Spring Harbor Laboratory (CSHL), a private, not-for-profit biomedical research laboratory, is collaborating with British drug maker GlaxoSmithKline (GSK) to develop a treatment for obesity and type 2 diabetes.
Scientists at CSHL and GSK will pursue drug development based on a novel approach to regulate the enzymatic activity of the phosphatase PTP1B in a collaboration slated to last about three years. The objective is to identify potent, selective, orally bioavailable small molecules that inhibit PTP1B activity in vivo following stimulation by insulin and leptin. The resulting drug would be designed to overcome the insulin and leptin resistance encountered in diabetes and obesity.
Both organizations will provide project co-leadership across different sets of expertise. This will enable synergy to facilitate the development of novel therapeutics. There is a joint committee with equal representation from both organizations that meets regularly to discuss, evolve and carry out the research plan. Specific aspects of the collaboration are outlined and agreed for each party, drawing on the strengths of each science team and organization: CSHL’s in-depth target knowledge and GSK’s drug discovery and development expertise.
According to Teri Willey, vice president for business development and technology transfer at CSHL, the relationship developed over time through visits and discussions among CSHL and GSK scientists to explore the science at CSHL and GSK sharing its capabilities and ideas. CSHL is “striving to achieve mutually beneficial and effective collaborations to accelerate research and develop new therapies to benefit patients,” she said.
“We’ve done long-term relationship-building based on the science and the scientists at both organizations,” Willey tells DDNews. “Though we engage our counterparts in business development at companies and look for ways to support good partnerships, these collaborations evolve because of the excellence of our scientists and the science at CSHL. Importantly, the most disruptive and interesting science and collaborations come through fundamental and basic research which is our focus at CSHL.”
Dr. Nicholas Tonks, an expert on the protein tyrosine phosphatase (PTP) family of enzymes and their roles in human diseases, will take the lead on the work at CSHL. He is considered a pioneer in the PTP field, having discovered PTP1B and done instrumental work in establishing the importance of the PTP family of enzymes as regulators of how cells respond to stimuli from their environment and as potential therapeutic candidates for several human diseases.
According to Carolyn Buser, global head of The Discovery Partnership with Academia program (DPAc) at GSK, “combining the in-depth target and disease knowledge of renowned academic groups with our drug-discovery expertise and capabilities can foster innovation and speed up the discovery and development of new medicines,” adding that GSK is “excited to expand our partnerships in North America and looks forward to working closely with Dr. Tonks, whose deep understanding of protein tyrosine phosphatase biology will complement our own work in this field.”
According to Buser, DPAc at GSK “combines the insights and creativity of the academic world with GSK’s drug discovery expertise to turn innovative research into medicines that benefit patients.” GSK currently has 13 DPAc collaborations in place at academic research institutions in North America and Europe.
The organizations hope that the collaboration will go all the way toward creating a viable drug, with GSK becoming more involved as a candidate moves toward and through the clinic, Willey added. If a candidate becomes a product, CSHL would receive license fees, milestones and royalties.

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