St. Michael's to investigate new treatments for prevention of brain injury complications

St. Michael's Hospital has been awarded up to $700,000 from the Federal Economic Development Agency of Southern Ontario to investigate new treatments to prevent complications following certain brain injuries.

The funding, to be administered by the Ontario Brain Institute, is part of an $11 million package announced by the federal government to help accelerate the commercialization of neurotechnologies.

The FedDev funds will be matched by Edge Therapeutics, Inc., a biopharmaceutical company based in New Jersey.

Edge and St. Michael's are exploring new ways of delivering nimodipine, an oral drug that has shown good results in preventing vasospasm, a major complication of aneurismal subarachnoid hemorrhage (bleeding in the area between the brain and the thin tissue that covers the brain).

For two weeks following a subarachnoid hemorrhage, patients are susceptible to cerebral vasospasm, which limits blood flow to the brain and can cause ischemic strokes and additional tissue damage. Nimodipine inhibits calcium ion transfer into smooth muscle, thus preventing contraction of smooth vascular muscle in the brain.

Subarachnoid hemorrhage affects 10 in 100,000 people in North America each year, or about 40,000 cases a year. More than 70 percent of patients with subarachnoid hemorrhage will either die or live permanently disabled 30 days after the incident.

Health Canada does not currently approve any highly effective treatment to prevent delayed cerebral ischemia (insufficient blood flow to the brain) and improve patient outcomes after an aneurismal subarachnoid hemorrhage or other traumatic brain injury, said Dr. R. Loch Macdonald, head of neurosurgery at St. Michael's.

Oral nimodipine is approved for aneurismal subarachnoid hemorrhage but is only marginally effective and overall outcomes are still poor, he said. Higher oral doses may be more effective, but there are safety issues and side effects such as low blood pressure, he said.

St. Michael's and Edge will collaborate on a Phase 2 clinical trial that would deliver nimodipine directly to the site of the brain injury through a biodegradable microparticle drug delivery system known as nimodipine microparticle formulation.

"Today, patients with brain hemorrhage face life-threatening delayed complications, and only marginally effective treatment options are available," said Dr. Macdonald. "This research collaboration will allow us to further advance a much-needed therapy."

The principal investigator is Dr. Julian Spears, co-director of the neurovascular program at St. Michael's. The clinical trial will be managed by the Applied Health Research Centre (AHRC), an academic clinical research centre led by Dr. Muhammad Mamdani and based at St. Michael's.

"This novel partnership spanning academia, industry and government will accelerate development of promising technologies and bring them to the market more quickly," said Dr. Arthur S. Slutsky, vice-president of research at St. Michael's.

According to Edge President and CEO Brian Leuthner, the microparticle system allows sustained, consistent release of nimodipine over the 14 days following initial injury. By delivering the drug directly to the injury site, much higher concentrations can be used.

In a Phase 2 clinical trial, an experimental drug or treatment is given to a large group of people (100-300) to see if it is effective and to further evaluate its safety.

St. Michael's will start enrolling patients in the Phase 2 clinical trial next year. Doctors here will deliver the drug to the brain injury site through endovascular coiling, a minimally invasive procedure in which a catheter is

Source: St. Michael's Hospital