Scientists at Columbia University who are working to combat injury-related depression, substance abuse, and suicide due to unremitting, persistent pain have discovered a powerful analgesic dubbed N60 that leads to neither tolerance nor addiction. The research team, led by Richard Ambron, PhD, professor of pathology and cell biology at Columbia University Medical Center, began to develop N60 after colleague Ying-Ju Sung, PhD, assistant professor of clinical pathology, discovered the pathway that neurons use to inform the brain of an injury. Left uncontrolled, this pathway persistently alters the electrical properties of the neuron, ultimately causing chronic pain. The Columbia team found that a specific protein in the pathway, called PKG, acts like a switch. As long as the switch is on, the pathway is activated and the brain continues to receive signals that are perceived as pain, even after an injury has healed.

Sung and Ambron quickly realized that PKG would be an excellent target for drug development. Since PKG is specific for biochemical signaling involved with chronic pain, shutting off PKG will not prevent a patient from feeling fresh injuries. It also operates in the peripheral nervous system, rather than the central nervous system, so a drug that blocks PKG does not have to cross the blood-brain barrier. Once they understood the function of PKG, the team began to work with medicinal chemists at Columbia to design a compound that would block PKG from sending signals to the brain. They discovered N60 to be a powerful and selective PKG blocker.

“We found in PKG a well-defined target that has been implicated in several types of pain that are particularly refractory to treatment,” Ambron says. “Now, we have an excellent inhibitor of the target which imparts no evident toxic or behavioral side effects and which also alleviates chronic pain in animal models of nerve injury and inflammation. N60 is non-addictive and non-sedative, and a single dose attenuates pain for at least 24 hours.”

The team has manufactured pharmaceutical-grade compound for studies to evaluate the safety of the drug. “We’ve got the drug, we’re confident in its efficacy, and we are actively looking for investors and experienced partners to help us put this through clinical testing,” says Jerry Kokoshka, a representative from Columbia Technology Ventures, the university’s TTO.

Source:  Columbia Technology Ventures

Posted July 28th, 2010 under Tech Transfer

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