New Duke-RTI collaborations explore drugs to combat chronic pain, cancer

January 2, 2019

This fall, Duke CTSI Accelerator and RTI International launched a new joint program to advance drug discovery research by combining the strengths of each institution. Now they’ve selected three projects to receive funding from the inaugural cycle of the Duke-RTI Collaborative Translational Research Grant.

“We’re very excited to support drug discovery collaborations that have great potential to improve people’s lives,” says Tarun Saxena, Program Leader at Duke CTSI Accelerator. “It speaks to the fantastic breadth of expertise and capacity at both Duke and RTI that we received such outstanding proposals in the first year of this initiative.”

Andrea Nackley DukeAndrea Nackley, PhD, Associate Professor in Anesthesiology at Duke, was motivated to apply for the Duke-RTI grant by her interest in improving the way we manage chronic pain, a longstanding issue that has been thrust into the public eye by the opioid crisis.

People with chronic pain conditions, such as lower back pain, are currently treated using analgesic drugs (NSAIDs like aspirin or ibuprofen, corticosteroids, and opioids). These medications target pain receptors in the central nervous system, which mean they come with a host of potential adverse side-effects, including addiction and altered mental states.

Nackley’s lab has identified a receptor that is peripheral to the nervous system and hasn’t been targeted by traditional pain relievers—they believe it holds promise for treating pain more effectively and without unwanted side-effects. But to find out if this approach will work, they need additional expertise in the medicinal chemistry aspect of drug development.

“It’s my goal to see this basic science translated into the clinic, but my lab is not in the drug design business,” Nackley explains. “Partnering with RTI makes sense because they have that expertise.”

She connected with Allison Zarkin, PhD, an organic chemist who works as a Research Associate at RTI International. Together they applied for and won the grant.

“It’s really exciting to make connections between scientists at Duke and scientists at RTI,” Zarkin says. “Andrea’s lab has done a lot of groundwork demonstrating that this receptor is a viable target for pain. But, because there hasn’t been much medicinal chemistry research done on the target, there’s room to develop molecules with improved properties.”

The funding from this grant will support Nackley and Zarkin as they develop the compound and run preclinical trials to discover if it has the intended effects. Meanwhile, they’re already looking ahead at the regulatory and commercial pathways that can take a new drug from the lab into the real world, where it can help people suffering from chronic pain.

“We want to understand what the milestones are, so that we can have the whole process in mind going forward,” Nackley says.

The 2018-19 Duke-RTI Collaborative Translation Research Grant winners are:

A new peripherally-restricted Adrb3 antagonist for the treatment of chronic pain and inflammation
Andrea Nackley, Duke University School of Medicine
Allison Zarkin, RTI International

Development of a novel ERRa antagonist for the treatment of cancer
Donald McDonnell, Duke Department of Pharmacology and Cancer Biology
Rangan Mitra, RTI International

Development of lead compounds directly targeting a newly discovered mechanism of central nervous system invasion in acute lymphoblastic leukemia
Dorothy Sipkins, Duke University School of Medicine
Trevor Price, Duke University School of Medicine
Danni Harris, RTI International