UConn School of Medicine's stroke drug is one step closer to clinical trials after receiving a follow-up research grant award of more than $2 million from the NIH’s National Heart, Lung, and Blood Institute (NHLBI). The small-molecule drug has demonstrated the ability to reduce damage and restore function after stroke in laboratory settings.
Novel P2X4 Receptor Inhibitor
The experimental, brain-permeable, anti-inflammatory therapy targets the P2X4 receptor, which is implicated in ischemic stroke damage. The innovative approach works by inhibiting the receptor to stop and reduce the expansion of brain damage caused by a stroke. Ischemic strokes, which constitute the majority of stroke cases, occur when a blockage in an artery leading to the brain reduces blood flow and oxygen, leading to brain cell damage or death.
"This renewed NIH grant funding will enable us to further advance our laboratory testing and ultimately apply to the FDA for an Investigational New Drug (IND) application. If approved, it will lead to first-in-human testing," says Dr. Bruce T. Liang, cardiovascular physician-scientist at UConn School of Medicine.
Mechanism of Action and Potential Benefits
When brain cells are damaged during a stroke, they release excessive amounts of adenosine triphosphate (ATP), which over-stimulates the P2X4 receptor, primarily found on immune cells in the blood and brain. Overactivation of the P2X4 receptor causes a cascade of detrimental effects in brain cells, leading to a larger stroke. UConn's medication crosses the blood-brain barrier to block this receptor.
According to Rajkumar Verma, assistant professor of neuroscience at the Calhoun Cardiology Center, the medication reduces brain damage, enhances the possibility for both short-term and long-term stroke recovery and restored function, and expands the time window available for stroke treatment.
Preclinical Evidence and Future Directions
Initial phase 1 funding from the NIH allowed the UConn research team to screen for and discover the experimental chemical, which has proven effective in animal models. The drug has shown neuroprotective properties and the ability to heal brain damage caused by stroke by reducing inflammation. If proven successful in animal models for safety and then in human clinical trials, the research team believes this neuroprotective drug intervention would have a groundbreaking impact on the future of stroke patient care.
The team's latest research findings were recently published in the Journal of the American Heart Association (JAHA).
This research was initially supported by the NIH via a small business “STTR phase 1 grant: A New Anti-inflammatory Therapy for Ischemic Stroke” grant to the UConn Technology Incubation Program (TIP) start-up company Provascor Pharmaceuticals.
