Damage-Reducing Stroke Drug from University of Montana Spinoff, Sinapis Pharma, Moving To Human Trials

University of Montana researchers have learned that low doses of methamphetamine given to rodents after strokes reduce brain damage and impairment by 50 percent or more. Now a UM research spinoff company, Sinapis Pharma , intends to start human Phase I clinical trials of the drug application in coming months.

“We have had fabulous results with rodent models,” said David Poulsen, a research associate professor in UM’s Department of Biomedical and Pharmaceutical Sciences and chief scientific officer for the new company. “If we have comparable results with people, this could become the standard of care.”

On the street, meth is a dangerous, addictive illegal drug. However, the Food and Drug Administration first approved prescription methamphetamine for clinical uses in 1944, and now it is used to treat attention deficit hyperactivity disorder, obesity and narcolepsy. Poulsen and his postdoctoral student Tom Rau have since discovered the protective effect of low-dose meth for strokes.

“The drug already has been approved for treating ADHD in children and obesity in adults as an oral dose,” Poulsen said. “What we are doing is giving the drug in an IV form, so this is a new formulation that’s being administered for a new application – stroke. This has never been done before.”

Sinapis Pharma will file an Investigational New Drug application with the FDA in February, and Poulsen expects Phase I trials to begin shortly thereafter and be completed by summer. During the trials, researchers test the new drug on a small group of people (20 to 80) to evaluate its safety, determine dosage and identify side effects.

“Basically we give them the drug in an IV and draw blood from them every couple of hours and monitor their blood pressure and heart rate and such,” Poulsen said.

He expects the Phase I trials to go smoothly because methamphetamine has been around a long time, and there is a lot of documentation about what humans can and can’t handle. “We don’t have to deal with a lot of the steps and hurdles encountered with the development of a new drug,” he said.

If Phase I goes well, the process will move to Phase II, when patients experiencing strokes at hospitals will be asked to give informed consent to test the drug.

“Some people will say no, and some will say yes, and some won’t meet the criteria,” Poulsen said. “We are talking about hundreds of patients for this kind of trial, so we would do it at large metropolitan areas across the United States, but I would like St. Patrick Hospital (and Health Sciences Center in Missoula) to be one of the places we recruit patients. I know I would want the drug if I was having a stroke.”

The researcher hopes to start Phase II trials by the end of the year.

About 60 different drugs have been tested as neuroprotective agents over the years, and they all have failed. Poulsen said this is because a cascade of pathological events occurs during a stroke, and most of those drugs target only one event, which is insufficient to tip the balance to protection.

“In order to have good therapeutic efficacy, you have to affect multiple targets,” he said. “Well, it turns out that is what methamphetamine is doing. It’s affecting inflammation, cell death, excitotoxicity. It’s clearly hitting multiple targets.”

Poulsen has scores of multihued images on his computer showing how rodent brains that have suffered stroke look when treated with methamphetamine versus those that didn’t receive the drug. Whether the drug is administered immediately, six hours or even 12 hours after the stroke, the reduction in damage is striking and clearly visible.

The researchers also gauge the functional dexterity of the animals with tests such as measuring how long it takes them to walk across a beam or pull adhesive tape off their paws. The animals that have had strokes and received the drug do significantly better on the tests.

Poulsen said trying to take his research from the lab to the business world has been quite an adventure. While working at St. Patrick Hospital in the Montana Neuroscience Institute, a collaboration between UM and the hospital, he met two surgeons, Nick Chandler and Peter VonDoersten, who became principal owners of Sinapis Pharma. Chandler chairs the new company and has since moved to Jacksonville, Fla.

“Right now we are basically a virtual company,” Poulsen said. “I’m doing the research aspects, and Nick’s in Florida managing things. Our CEO, Don Picker in New Jersey, is a serial entrepreneur who has taken several drugs through the process and moved them to market. Al Henry, our chief financial officer, is in Chicago and has run several venture capital funds that were focused on the life sciences and drug development. So we are spread all over.”

He said $350,000 in “critical” state funding from the Montana Board of Research and Commercialization Technology allowed them to generate the preliminary data to reach this point. Sinapis also has raised about $500,000 in private equity to fund Phase I trials. If the process continues successfully, the company will need another $6 million to $8 million for Phase II trials.

UM has a standard formula for any royalties generated by its intellectual properties such as the new drug application: Half goes to the faculty inventors and half to the University. And of UM’s share, one-third of that is made available to enhance the inventors’ campus research operation.

But will there be any royalties? Poulsen admits it’s still a long shot at this point.

“But our whole goal is to try to create startup companies that stay here in Montana,” he said. “This has been fun. I get as excited about the business of science as the science of science. It’s exciting to have the chance to develop something that actually gets into the clinic and changes lives.”

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