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UM researchers awarded $1M to study use of meth to limit brain injury impacts

Missoulian.com, September 16, 2013

An accidental discovery by a University of Montana researcher may soon lead to the clinical testing of a new drug that limits the impacts of traumatic brain injury and reduces post-traumatic epilepsy in rats.

Research professor Dave Poulsen and members of his team in the Department of Biomedical and Pharmaceutical Sciences found that low doses of methamphetamine reduced brain damage in rats after a traumatic brain injury or stroke.

The U.S. Army last month awarded Poulsen $1 million to further test the drug. The team will soon learn if the project wins an additional $6 million from the Joint Warfighter Medical Research Program – funding that would place the drug on the fast track toward clinical testing in human patients.

“It’s huge,” Poulsen said last week in his office. “This would be the first human clinical trial that’s been funded through UM.”

Armed with a litany of scientific papers citing the neurotioxic dangers of methamphetamine, Poulsen set out to analyze the drug in 2006.

Previous research had focused on high and repeated doses of meth, such as those taken by addicts. At the same time, Poulsen knew, the FDA had approved low doses of methamphetamine to treat various disorders, including ADHD in children 6 years and older.

Poulsen analyzed a range of methamphetamine doses and their impacts in rat models that had suffered strokes. They found that at high doses, the drug made the stroke worse, but at low doses, it became neuroprotective – beneficial to the rat.

But what was the right dose and when did it need to be administered to be beneficial? Theoretically, Poulsen said, a human patient can receive one milligram of methamphetamine for every one kilogram of weight and remain within FDA dosing guidelines. In their rat model, however, they found that neuroprotective benefits began at levels far below the FDA limit.

“We’ve identified a plasma drug level that’s needed to achieve a therapeutic effect,” Poulsen said. “If you model that into humans, at that dose, you’re only giving a 70 kilogram patient 18 milligrams. It’s not one-to-one.”

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Poulsen described most brain injuries as cascading events that affect multiple areas of the brain – something most drugs are ill-equipped to address. What the research team needed was a drug that covered as many events as possible shortly after a brain injury occurs.

They believe they’ve found that in methamphetamine.

“It’s like a bucket with

12 holes in it,” Poulsen said. “You stick your finger in one and the 11 others leak out. To be therapeutically effective, you have to have a drug that hits multiple pathways, and to our surprise, that’s what this does.”

In 2011, the U.S. Army gave Poulsen $1.5 million to determine the lowest effective dose and identify the therapeutic window during which the drug can be administered following a traumatic brain injury.

The award also examined the ability of low-dose methamphetamine in preventing or reducing post-traumatic epilepsy. The team received an additional $1 million from the Army last month to further develop the drug.

“The military eventually wants a drug that can be administered to soldiers exposed to blast-force energy waves from explosions,” Poulsen said. “Such therapies would be applied within hours of exposure to a significant blast.”

Funding from the Joint Warfighter Medical Research Program could speed up testing and development of the drug. The UM spin-off company, Sinapis Pharma – founded by Poulsen and partners in 2009 – is looking to bring a low-dose methamphetamine product to the market.

“Over the last 15 years, the university has been evolving more to a culture of research,” Poulsen said. “We’ve come to a point now that we’re not doing basic discovery science, we’re actually doing preclinical development and moving drugs and products into clinical work and actually benefitting patients.”