A mistake made by a PhD student in a University of Montana lab nearly a decade ago is now on the brink of mid-stage clinical trials as a potential treatment for traumatic brain injury.
And, most surprising of all, the treatment consists of a small dose of methamphetamine.
It all started when a research assistant in David Poulsen‘s neuroscience research lab was doing an experiment that involved using high doses of methamphetamine to create brain damage in small animal models. But somewhere along the line, he misread one of the concentrations of meth that he was preparing and accidentally gave a dramatically diluted dose to one group of rats.
When the team later processed the brain specimens, they found that one group of rats was mysteriously neuroprotected. It was the group that had mistakenly received a small dose.
Poulsen’s team took that discovery and ran with it, spending the next several years applying for grants and studying how it was possible that a drug so dangerous to the brain in high doses could be so beneficial in low doses.
Actually, medical meth has been in use for quite some time. It was used in the 1930s to treat asthma and narcolepsy, and during World War II to keep pilots awake. Today, a low dose is used in the ADHD drug Desonyx.
Dr. James Fonger, a heart surgeon who’s CEO of the venture that’s commercializing the lab’s work, said it has to do with dopamine. “At high doses, there are a couple of well-known receptors in the brain which get hit by the drug and cause damage. Underneath that, there’s dopamine receptors that are completely overwhelmed at high doses and have no effect,” he explained. “But if you only mildly stimulate the dopamine receptors, they are very neuroprotective.”
With method of use patents from University of Montana, Buffalo-based Sinapis Pharma is commercializing low-dose IV methamphetamine as a new way to treat traumatic brain injuries, potentially up to 12 hours after they occur.
TBI is an appealing market for the neuroprotective treatment because there’s currently no therapeutic treatment out there. “It’s a little bit like what we used to do with people who had a heart attack or conventional stroke, which was put them to bed and hope they get better,” Fonger said.
Fonger sees the TBI treatment paradigm shifting in the same way that it did in cardiac care in the 1970s and 1980s. Now, he said, cardiologists have a whole library of things they can do after someone has a heart attack to both fix structural heart problems and prevent future heart attacks.
Although some work has been done toward finding a treatment, the field has struggled to translate promising research into approved therapies. A short window for intervention and the feat of getting drugs across the blood-brain barrier have proved challenging. And that short window of intervention has also made it hard to carry out the protocols of clinical trials.
But the FDA has made some recent changes to the design of clinical trials that Fonger is encouraged by. And he’s convinced Sinapis’s approach is different than others tried in the past because its neuroprotective effect has multiple pathways and a long therapeutic window. “Other drugs, to have their effect, have to be given within three to four hours after injury,” Fonger said.
Not to mention it’s cheap to make, stable on the shelf and easy to manage, he added.
Now it’s time to show that it works. With phase 1 safety studies complete, Sinapis is in the middle of raising a $6 million Series B that will fund an upcoming trial in 30 patients with brain injuries, which will establish dosing for the subsequent Phase 2b efficacy study. That one will include 400 patients and is slated to begin in 2015, Fonger said. It will cost a lot of money, too, but he’s hopeful about “significant” interest he’s seen at the professional sports level and by the NIH and Department of Defense.
“We’re hopeful that a large part, if not all of the funding for the 400-patient trial, might actually be non-dilutive because of the unique position of a brain injury drug,” he said, pointing out that athletes and soldiers are common victims of concussions.
If treatment succeeds in Phase 2b, it would advance to Phase 3. But by then, it would ideally have backing from a Big Pharma partner.
“It’s a big swing for the fences,” Fonger said, “but people have got to step up and do these things.”
[Image credit: Breaking Bad Wiki]