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The Search To End Pain Takes A New Direction As Stony Brook Research Prompts New Interest

Jan 19, 2007 - 2:45:38 PM

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STONY BROOK, N.Y., January 19, 2007—The recent discovery of young children in three related families in northern Pakistan who are unable to sense pain has stirred hopes for a new class of painkillers. A research study of the children found that they shared a mutated gene called SCN9A that encodes a channel permitting the passage of sodium through cellular membranes—a pathway that had been previously linked to the process of pain signaling by Stony Brook University researchers. The researcher who led the recent study of these children said the research provides “an exciting new target for painkilling drugs.”

But the drug may already be on the way.

Ten years ago, in a basement laboratory at Stony Brook, a group of researchers embarking on one of the first interdisciplinary collaborations of its kind, developed what they thought would ultimately provide a cure for pain. The university licensed the research to a pharmaceutical company, but general interest in the development of a drug directed against sodium to ease excruciating pain has languished—until now.

In the early-1990s, Simon Halegoua, Professor of Neurobiology at Stony Brook and presently Director of its Brain and Spinal Cord Research Center, teamed with molecular biologist and Howard Hughes Investigator Gail Mandel and electrophysiologist Paul Brehm, both Professors of Neurobiology at Stony Brook at the time (and currently at the Vollum Institute in Portland, Oregon) to explain how electrical signaling was regulated in the peripheral nervous system. Working over the course of several years, Halegoua focused on the cell biology of the signaling process; Mandel concentrated on the molecular biology; and Brehm carried out the electrophysiological characterization of the sodium channels.

 Because their labs were located on different floors, they decided to move to the basement of the Life Sciences Building, which they renovated to create a physical space conducive to daily intellectual interactions. Back then, the idea of researchers from different fields combining individual expertise across disciplines to create a new body of knowledge was relatively unheard of—but the word “interdisciplinary” is now standard in research lexicon. Their interdisciplinary research resulted in a series of publications that culminated in the cloning of the first sodium channel in sensory nerves and published in the Proceedings of the National Academy of Sciences, USA in 1997.

They predicted that the novel sodium channel was involved in the transmission of pain and suggested that a drug aimed at blocking this channel would control pain.  This unexpected discovery led to the Stony Brook patent, but there was no proof this could be useful in humans until the children in Pakistan were found.

The potential for such a drug is “enormous,” according to Halegoua and Mandel. “The discovery of the Pakistani children has accelerated interest for developing scientific blockers for this particular sodium channel.”
 
Their research raised many possibilities—the reduction or elimination of pain for patients who have cancer, arthritis, migraine headaches, muscle pain, pain from burns, and pain from all sorts of debilitating diseases. It also raised the possibility of replacing opiates or morphine—along with their significant side effects—as the century-old standard therapy for eliminating extreme pain. Blocking the sodium channel in humans could conceivably produce an analgesic that virtually eliminates pain, which often complicates treatment, especially in the very young and the very old.

A patent for their research was issued in 2002 and licensed to Trophix Pharmaceuticals Inc., a biotechnology company headed by Jeffrey McKelvy, a former Stony Brook Professor. Icagen, Inc. a small pharmaceutical company, reported earlier this week, on January 10, that it now holds an “exclusive license to various patents and patent applications which originated from work carried out at the State University at Stony Brook.” Icagen said it had already identified selective compounds, which demonstrate effectiveness in animal models for neuropathic and inflammatory pain.

While Halegoua, Brehm and Mandel subsequently moved to premier labs in the university’s primary research building, the state-of-the-art Centers for Molecular Medicine, the humble beginnings opened up a new field of research that translated into a potential cure for pain.

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