New Chronic Pain Treatment Could Replace Addictive Opioids

AUSTIN, Texas — A revolutionary new chronic pain treatment avoids using opioids, a highly addictive class of drugs, a new study reveals. The opioid epidemic has ravaged American society, as 645,000 people died from overdoses between 1999 and 2021, according to the Centers for Disease Control and Prevention. Now, researchers from the University of Texas at Austin, the University of Texas at Dallas, and the University of Miami have identified a novel molecule, FEM-1689, offering significant promise in the treatment of neuropathic pain, a condition affecting millions globally.

Neuropathic pain, a complex and chronic condition, stems from nerve damage in various body tissues, leading to symptoms like electric shocks, tingling, burning, or stabbing sensations. Commonly associated with conditions like diabetes, multiple sclerosis, and the aftermath of chemotherapy or physical injuries, this type of pain has been notoriously challenging to treat. Traditional pain medications frequently fall short in effectiveness and carry the risk of serious side-effects, including addiction.

The study highlights the effectiveness of FEM-1689 in reducing hypersensitivity in mouse trials. This molecule works by targeting a specific protein implicated in neuropathic pain.

“We found it to be an effective painkiller, and the effects were rather long-lived,” says study co-corresponding author Stephen Martin, the June and J. Virgil Waggoner Regents Chair in Chemistry at The University of Texas at Austin, in a university release. “When we tested it on different models, diabetic neuropathy and chemotherapy-induced neuropathy, for example, we found this compound has an incredible beneficial effect.”

FEM-1689 does not interact with opioid receptors, a significant step away from the risk of addiction associated with many current pain medications. It also plays a role in regulating the integrated stress response (ISR).

ISR is a complex network of cellular signals that helps the body respond to injuries and diseases. Effective regulation of ISR is crucial for restoring balance and promoting healing, while dysregulation can lead to various diseases, including cancer, diabetes, and metabolic disorders.

“It’s our goal to make this compound into a drug that can be used to treat chronic pain without the dangers of opioids,” notes Martin. “Neuropathic pain is often a debilitating condition that can affect people their entire lives, and we need a treatment that is well tolerated and effective.”

NuvoNuro Inc., a company co-founded by Martin and other study authors, has received a grant from the National Institutes of Health HEAL Initiative, dedicated to finding scientific solutions to the national opioid crisis. This funding is a critical step towards the clinical development of a drug based on FEM-1689.

“This work is the culmination of a wonderful five-year collaboration with our colleagues at UT Austin and is a great example of academic drug discovery pushing the field of non-opioid pain therapeutics forward,” explains study co-corresponding author Theodore Price, a professor of neuroscience at The University of Texas at Dallas. “Our funding from NIH on this continuing project through our spin-out company, NuvoNuro, has the potential to take us toward clinical development in the next few years, which is extraordinarily exciting.”

This research was funded by the National Institutes of Health, Natural Sciences and Engineering Research Council of Canada, and the Robert A. Welch Foundation.

The study is published in the journal Proceedings of the National Academy of Sciences.