Washington Research Foundation (WRF) has awarded a $249,950 technology commercialization grant to a team led by Marco Pravetoni, Ph.D., a professor in the University of Washington’s Department of Psychiatry and Behavioral Sciences, holder of the Rick L. Seaver Endowed Professorship for Brain Wellness, and director of the Center for Medication Development for Substance Use Disorders. This new award follows the successful completion of previous WRF assistance from a $94,029 grant in 2023 to support discovery of new treatments to address fentanyl-related overdoses.
Since 2000, more than 500,000 people in the United States have died from opioid-related overdoses. Today, nearly 70% of all fatal drug overdoses in the U.S. are linked to fentanyl—a potent synthetic opioid—and its analogs. While emergency treatments like naloxone (Narcan) and nalmefene (OpVee) are lifesaving medications, they may not always be effective, especially in cases involving highly potent and long-lasting synthetic opioids. Increasing the treatment dosage or administering multiple doses can improve outcomes, but it also raises the risk of triggering severe withdrawal symptoms. There is an urgent need for new overdose treatments that are effective, have fewer side effects, and may be combined with current treatments.
A team led by Pravetoni is developing a promising new treatment addressing fentanyl-related overdoses. The treatment is based on single-chain variable fragments (scFvs), which are small, lab-engineered proteins originally derived from the active parts of antibodies that recognize and bind specific targets. By keeping only the essential binding regions of the antibody, the smaller scFvs can target molecules like fentanyl with high precision while being easier to produce and modify. Pravetoni’s team is designing scFvs that bind tightly to fentanyl and similar opioids in the bloodstream, blocking them from reaching the brain’s opioid receptors. Because these fragments are highly selective and do not interfere with existing treatments like naloxone, they offer a lower risk of side effects or drug interactions. Early studies in mice have shown that these engineered proteins can effectively reverse fentanyl overdoses, and that scFv can be combined with naloxone, potentiating its effects.
With support from the previous WRF grant, Pravetoni’s team successfully identified a lead scFv candidate with the stability and biophysical properties needed for large-scale manufacturing. They also showed that this scFv could reverse fentanyl overdoses in mice in a dose-dependent way, and whether used alone or with naloxone. With this next round of funding, the team plans to further improve the design and production process of the scFv to prepare for clinical manufacturing. They will also create drug formulations that are suitable for emergency use in the field and compatible with commercial delivery devices. Under this new WRF award, the team will collect more preclinical data to show how well these formulations work, how they behave in the body, and how they might work together with naloxone to improve overdose treatment.
“I am very excited about the potential for these new treatments to make a change in people’s lives,” said Pravetoni, who came to the University of Washington from the University of Minnesota Medical School in 2021. “Since moving to Seattle, WRF and Dr. Antia have been wonderful partners in supporting our work.”
