By Seizing the Risk, The Michael J. Fox Foundation Helps Awardees Secure Funds Needed to Develop Novel Parkinson’s Drugs
The path to new drugs often begins with a Eureka moment — when an academic working in a lab discovers a specific molecular process in our cells that seems to be causing a disease or its symptoms. It’s a key first step toward developing drugs that work by targeting such processes.
For Jeff Conn, PhD, of Vanderbilt University, that stroke of brilliance came in 1998, when his team identified a glutamate receptor called mGluR4 that, when activated, seemed to reduce the activity of a particular part of the brain that becomes overactive in people with Parkinson’s disease (PD).
The “aha” moment for Jim Surmeier, PhD, of Northwestern University, came in 2006. His research led him to theorize that calcium channel blockers (such as certain high blood pressure medications, or new drugs like them) might slow or even stop the progression of PD.
Hurdles and Potholes
Unfortunately, while discoveries like those made by Conn and Surmeier provide the genesis for most new therapies, they’re merely the first step along a drug development road lined with myriad hurdles and potholes. On average, the time it takes to bring one new drug to market is 15 to 30 years, at a cost of $1 billion. And this is for those few compounds that actually make it to pharmacy shelves. Most potential treatments die early, in what is known as the “Valley of Death,” that period of research when an idea born in a university setting loses steam, and is unable to secure the necessary support from the pharmaceutical industry to move research from the laboratory and into the clinic.
Conn and Surmeier, like most academic researchers in their shoes, knew that without a push from the right source, their ideas risked falling prey to this challenging system. They knew that their novel drug targets might die before they ever exited the Petri dish.
So both scientists, searching for the right engine to drive their research forward, came to MJFF. And the Foundation was willing to take a risk on both, stepping in where other funders wouldn’t.
Great Potential and Calculated Risk
“When we came to MJFF, we had a compelling idea for a Parkinson’s drug based on basic science,” says Conn. “But it was way too early on for any company to invest in our approach. We needed another source to help us test our hypothesis, to make it more attractive to industry investment. MJFF was that source.”
In reviewing Conn’s science, MJFF saw great potential, and was willing to take a calculated risk to fund studies that could drive his approach closer to testing in humans. Since 2005, MJFF has invested nearly $5 million in Conn’s pursuit of a potential new class of PD drugs targeting mGluR4.
Like Conn, Surmeier came to the Foundation for support of pre-clinical studies based on the premise that calcium channel blockers might slow the progression of PD. The data was promising. Surmeier has now identified a new drug class that blocks the calcium channels he believes are responsible for stressing dopamine neurons.
A Phase II clinical trial, in which MJFF invested $2.1 million for an existing calcium channel blocker called isradipine, recently returned positive safety results. This study team, led by Tanya Simuni, PhD, also of Northwestern University, is hoping to begin a Phase III efficacy study of isradipine in 2013.
Surmeier is optimistic about both isradipine and his new approach, which could provide an additional option for people with PD. While isradipine provided researchers with a fast way to test his theory (since the drug is already FDA-approved, it was quickly readied for clinical testing), ultimately, improved compounds that target PD specifically, such as Surmeier’s, may be needed.
“Without The Michael J. Fox Foundation, we never would have been able to move forward with the drug discovery effort,” says Surmeier.
New Opportunities and Next Steps
In 2012 the payoff of MJFF investment has been huge, for both scientists and their teams. In September, Vanderbilt announced a next step collaboration with Bristol-Myers Squibb for the ongoing development of mGluR4-targeted drugs. While it is impossible to predict how quickly the program will advance from this point, Conn is hopeful that an experimental drug could enter clinical testing as soon as 2013.
Surmeier has received significant government funding to move his new compounds closer to the clinic. In September, he was awarded one of only three multi-million dollar Blueprint for Neuroscience Research grants from the National Institutes of Health (NIH).
While there’s a long road ahead, Surmeier is hopeful that the NIH monies will allow him to move his drug through the Valley of Death toward a Phase I clinical trial in PD patients.
“If we can do this,” he says, “I’m sure that the necessary investment of industry will follow.”
“My hat is off to the Foundation,” says Conn. “Establishing this partnership is proof that MJFF can have a huge impact. We are very hopeful that these drug candidates will go the distance. Without the Foundation, they never would have even gotten off the ground.”