Relying on the success of preclinical experiments using metabotropic glutamate receptor antagonists (mGluRs) to treat mental retardation, Sention Inc. licensed a family of compounds from Merck & Co. Inc.

Sention signed an exclusive licensing and research collaboration agreement with Whitehouse Station, N.J.-based Merck to develop a preclinical mGluR5 antagonist for treating fragile X syndrome, an inherited form of mental retardation. Metabotropic glutamate receptors are targets in the central nervous system. Sention said abnormal signaling from the receptor might be the source of symptoms associated with fragile X.

"What Sention owned before this deal was the intellectual property for using an mGluR5 antagonist to treat fragile X mental retardation and other disorders, but we didn't have a compound ourselves," said David Mantus, vice president of regulatory affairs for the Providence, R.I.-based Sention.

The collaboration gives Sention "a fairly mature compound from Merck's portfolio, which we would then proceed to move into and through clinical development," he told BioWorld Today.

Financial terms of the deal were not disclosed, but Mantus said Sention is responsible for continuing the development of the compound into clinical trials. The company would have exclusive rights to the finished product for the specific indication of fragile X, though Sention would be allowed to develop the drug for Down syndrome, Mantus said. "We would also have an option to develop it for Huntington's disease."

The use of mGluR antagonists for treating mental retardation was suggested by one of Sention's founders, Mark Bear, a professor of neuroscience at the Picower Center for Learning and Memory at MIT.

Bear described the concept of linking "what we know to be the genetic disorder - the fragile X mental retardation protein - to the mGluR receptor. Then by antagonizing those receptors, you could potentially affect that process," Mantus said, adding that Bear demonstrated how the antagonists would work in preclinical models.

"Rather than treating symptoms, it's [targeting] what is thought to be the molecular basis of the disease," he said. "Dr. Bear did the fundamental science behind it. What makes it special is how interesting and fascinating the science is, and I believe that's also why Merck was interested in being part of this collaboration."

Sention, which was founded in 1999, focuses on developing treatments for central nervous system disorders, cognition and memory type disorders and mild cognitive impairment. The company also hopes to develop products for Alzheimer's disease.

Two products are in clinical trials for cognitive disorders: C105 is in Phase II trials and SN522 is in Phase I. Both drugs work by modulating neurotransmitters in the brain, Mantus said.

To date, the company has raised about $35 million through private financing, Mantus said. Its first financing round in March 2001 raised $13 million and was intended to get its lead products into clinical trials. (See BioWorld Today, Feb. 13, 2002.)

Sention has about 25 employees.

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