Ischemic stroke is the most common form of stroke in the U.S., affecting more than 690,000 people each year, according to the Centers for Disease Control & Prevention.
And while endovascular therapy and clot-busting treatments such as tPA (tissue plasminogen activator) or TNK (Tenecteplase) have come a long way over the past 25 years, they are available to limited number of patients. For example, tPA and TNK must typically be administered within 4.5 hours of symptom onset.
For acute ischemic stroke patients who cannot receive tPA or TNK within 4.5 hours or who aren’t eligible for clot-busting treatments, few treatment options are available to reduce brain injury.
The UC Gardner Neuroscience Institute has received $19 million in federal funding from the National Institutes of Health (NIH) to serve as the lead center for a Phase 2 clinical trial that will study the efficacy of a new monoclonal antibody treatment for those patients, possibly providing new hope for treatment and recovery for patients where time and access may have been limited.
“This new drug offers a lot of hope,” said study co-investigator Pooja Khatri, MD, MSc, associate director of the UC Gardner Neuroscience Institute. “The preliminary data suggest it will work better and faster to open clots that cause strokes in our patients, while protecting the brain from irreversible damage. It may also be safer, allowing us to give it to more patients. We are excited by the possibility of bringing the next tPA/TNK to the stroke field, carrying on the tradition of when Cincinnati led the way in developing and establishing tPA as the very first emergency treatment for stroke in the late 1980s and early 1990s.”
The SISTER (Strategy for Improving Stroke Treatment Response) study will administer the monoclonal antibody TS23 to acute ischemic stroke patients within between 4.5 and 24 hours of symptom onset.
Developed at the University of Arizona, TS23 works by blocking A2-antiplasmin, a protein in the blood that is a key determinant of whether blood clots dissolve. This will be the first time the treatment is administered to stroke patients, though previous studies among healthy volunteers and in animal models have shown promise in dissolving blood clots and opening up patients’ arteries more effectively than current treatments. It may also provide some neuroprotective properties and produce less hemorrhage and dead brain tissue.
The study is funded by the NIH National Institute of Neurological Disorders and Stroke (NINDS) and will be conducted within NIH StrokeNet. Enrollment is expected to begin nationwide in March 2024, and researchers expect to enroll 300 patients nationwide across 40 sites, including about a dozen patients in Greater Cincinnati.
“I am excited to lead this study with the UC team, that brings a great amount of expertise and experience in acute stroke clinical trials. The drug we are studying is very promising and has shown that it is safer and more effective than tPA in animal studies. tPA/TNK has improved stroke care drastically, but it is time we had a better player in the field. I hope that TS23 will bring that much needed next wave of innovation. With extended time window that we are testing this drug in, it has the potential to reduce the current disparities in stroke care,” said Eva Mistry, MBBS, MSCI, a physician-researcher affiliated with the UC Gardner Neuroscience Institute.
The trial will be led nationally by Khatri and Mistry. Khatri is professor, vice chair of research, and division chief in the Department of Neurology & Rehabilitation Medicine at the UC College of Medicine, and Mistry is associate professor in the Department of Neurology & Rehabilitation Medicine at the UC College of Medicine. Both are affiliated with the UC Gardner Neuroscience Institute, and Khatri is the institute’s associate director. The trial will be led locally by Dr. Yasmin Aziz, assistant professor in in the Department of Neurology & Rehabilitation Medicine at the UC College of Medicine.
Other national PIs are Guy Reed, MD, Dean of the College of Medicine at the University of Arizona – Phoenix and the developer of TS23; and Jordan Elm, PhD, professor of biostatistics in the Department of Public Health Sciences at the Medical University of South Carolina.
The UC Imaging Management Center, led by UC Gardner Neuroscience Institute neuroradiologist Achala Vagal, MD, will serve as the central imaging management system for the study. The center will receive all research-specific imaging and will also be responsible for providing central readings and analysis of specific scans.
The UC Gardner Neuroscience Institute is celebrating 10 years as the national coordinating center for all clinical stroke trials within the NIH StrokeNet, funded by the NINDS.
NIH StrokeNet conducts clinical trials and research studies to advance acute stroke treatment, stroke prevention and recovery and rehabilitation following a stroke. StrokeNet, which spans 27 regional stroke centers or hubs and nearly 400 enrolling hospitals, serves as the infrastructure and pipeline for new potential treatments for patients with stroke and those at risk for stroke.