Weill Cornell Medicine has received more than $635,000 in first-year funding for a two-year grant worth up to $1.24 million from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, to study a new approach for delivering an experimental non-opioid pain medication, called BP4L-18:1:1, to relieve neuropathic pain. The grant could be extended beyond its second year if the research achieves prescribed milestones.
People with neuropathic pain, which occurs when the nervous system itself is damaged, have few effective options to treat their pain, and current treatments are often minimally effective and are frequently associated with a poor side effect profile. The current grant aims to improve the efficacy of BP4L-18:1:1 by providing tissue-specific drug targeting. The new delivery system, if scientifically validated, could allow us to improve the drug’s efficacy and reduce the drug dose,” said principal investigator Dr. Peter A. Goldstein, a professor of anesthesiology at Weill Cornell Medicine and an anesthesiologist at NewYork-Presbyterian/Weill Cornell Medical Center, who for the past decade has been working with members of his laboratory, notably Dr. Gareth R. Tibbs, as well as through industry start-up Akelos, Inc. to develop the experimental therapy.
Dr. Peter Goldstein. Credit: Travis Curry
About 116 million adults in the United States live with chronic pain, and many of these people are prescribed opioids, which can lead to addiction and overdose. Neuropathic pain accounts for about 18 percent of these patients.
Opioids are typically not effective against neuropathic pain, which is driven in part by hyperactive neurons, a major cell-type within the nervous system. Prior research found that a group of proteins, called HCN ion channels, sit on these nerve cells’ outer membrane and help drive this hyperactivity.
The new grant will fund a study building on preclinical work finding that BP4L-18:1:1 blocks HCN1, the HCN channel most commonly found in human pain-sensing nerve cells. While the drug worked exactly as originally designed in a rat neuropathic pain model, the dose was relatively high, Dr. Goldstein said. Because HCN1 is also found in the brain, the researchers attached a chemical “anchor” to BP4L-18:1:1 to keep it from crossing the blood-brain barrier, helping to avoid potential central nervous system (CNS) side effects such as problems with memory or motor control.
The research team, which includes Dr. Tibbs; Dr. Paul Riegelhaupt, an assistant professor of anesthesiology from Weill Cornell; and Dr. Derek Tan of Memorial Sloan Kettering Cancer Center, now aims to identify a variant of a monoclonal antibody, to attach to BP4L-18:1:1 so that the drug can be delivered more precisely, possibly helping to lower the dose. While researchers don’t yet know whether the new version of the drug will cross the blood-brain barrier, the dose may be low enough to avoid CNS side effects, Dr. Goldstein said.
If the antibody works as hoped, “the next phase of research would be to study the drug in lab-grown cells and in animal models to see if the new molecule behaves exactly as we want and still relieves neuropathic pain,” Dr. Goldstein said.
Dr. Goldstein is a coinventor on patents, serves on the Scientific Advisory Board of Akelos, Inc., and holds an equity interest in the company. Dr. Tibbs is a coinventor on patents, serves on the Scientific Advisory Board of Akelos, Inc., serves as a consultant to the company, and holds an equity interest in Akelos, Inc.
