UM SOM Research Gathers New Evidence for Novel Stroke Treatment

Medicine Could Transform Treatment of Brain Swelling in Stroke

New research based on discoveries from the University of Maryland School of Medicine (UMSOM) provides further evidence that an innovative treatment strategy may help prevent brain swelling and death in stroke patients. J. Marc Simard, MD, PhD, Professor of Neurosurgery at the University of Maryland School of Medicine, along with colleagues at Yale University and Harvard Massachusetts General Hospital, found that Cirara, an investigational drug, powerfully reduced brain swelling and death in patients who had suffered a type of large stroke called malignant infarction, which normally carries a high mortality rate.

The findings were presented at the International Stroke Conference, held last month in Los Angeles, California.

“These results are quite promising,” says Dr. Simard, who is an esteemed physician-scientist and a clinical neurosurgeon. “We have a lot more work to do, but this approach could be an effective strategy for severe stroke patients who currently have no good treatment options.”

Previously, in October 2015, Dr. Simard and his colleagues, Kevin N. Sheth, MD formerly of UM SOM and now at Yale University, and W. Taylor Kimberly, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, also presented early data at the Neurocritical Care Society annual meeting, showing that the medication was effective in reducing brain swelling. Dr. Sheth is an Associate Professor of Neurology and of Neurosurgery, Division Chief of Neurocritical Care and Emergency Neurology, and Director of the Neuroscience ICU at the Yale School of Medicine. Dr. Kimberley is Associate Director of the MGH Neuroscience Intensive Care Unit at Massachusetts General Hospital, and is an Assistant Professor of Neurology at Harvard Medical School.

In stroke patients who were aged 70 or younger, the researchers found that at six months after the stroke, there was a three-fold reduction in overall mortality among patients who were given Cirara, and a ten-fold decrease in death from brain swelling among the Cirara group.

Swelling is a pivotal complication in many central nervous system ailments, including stroke, traumatic brain and spinal cord injuries, and others. In all of these conditions, the microvessels (capillaries) react to injury in a way that ultimately can be counterproductive, often leading to severe swelling of brain tissues that can be fatal. Dr. Simard and his colleagues discovered that in many of these conditions, the sulfonylurea receptor 1 (Sur1) plays a major, previously unrecognized, pathological role. It appears that Sur1 is involved in many of the most dangerous symptoms in these diseases, including cell swelling, cell death, breakdown of the barrier that normally protects the brain and inflammation. Dr. Simard and his colleagues have focused primarily on a drug called glibenclamide (a.k.a., Glyburide), which inhibits Sur1. Glibenclamide is a well-known, safe drug that has been in use for nearly 50 years to treat adult onset diabetes.

Cirara, which is made by New York City based Remedy Pharmaceuticals, is an exclusive intravenous formulation of glibenclamide.

“This new data shows a continued reduction in mortality and improvement in functional scores,” Sven Jacobson, MBA, the CEO of Remedy Pharmaceuticals. “The data further confirms the mechanism of action of Cirara.”

The researchers and Remedy are now planning to undertake a Phase 3 trial: the drug will be given to large groups of people to confirm its effectiveness and compare it to commonly used treatments.

“This work exemplifies how partnerships between academic research and private industry can yield potential breakthroughs,” said UM SOM Dean E. Albert Reece, MD, PhD, MBA, who is also Vice President of Medical Affairs, the University of Maryland and the John Z. and Akiko Bowers Distinguished Professor, University of Maryland School of Medicine. “We can have tremendous impact with clinical studies like this because they bring scientific advances directly to patients who benefit the most.”

About the University of Maryland School of Medicine

The University of Maryland School of Medicine was chartered in 1807, is the first public medical school in the United States, and continues today as a pioneering leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Maryland’s Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in cancer, brain science, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global presence, with research and treatment facilities in more than 35 countries around the world. medschool.umaryland.edu/

About Remedy Pharmaceuticals

Remedy Pharmaceuticals, Inc. is a privately-held, clinical stage pharmaceutical company focused on developing and bringing lifesaving treatment to millions of people affected by acute central nervous system (CNS) edema – including stroke, traumatic brain injury, spinal cord injury, as well as other ischemic injuries and neurological disorders.

ABOUT CIRARA™

CIRARA™ is a patented, high affinity inhibitor of Sur1-Trpm4 channels, discovered by University of Maryland School of Medicine neurosurgeon Dr. J. Marc Simard, MD, PhD, which is suitable for intravenous delivery at the bedside or in an ambulance.