Last fall in STAT, Matt Herper questioned whether the biomedical research enterprise is really laying the necessary groundwork to gain the full benefit of innovation in “biology’s century.” “The biggest looming problem is that… new technologies in biology [could] outpace our ability to assess them,” he observed. “Our goal, as a society, seems to be to manufacture more and more sports cars and to drive them faster and faster into the mud.”
Mike Milken has used a similar metaphor for systemic challenges in research: Building high-speed trains won’t get you far unless you also lay the specialized tracks they require. Over the past couple of decades, the Michael J. Fox Foundation has been working to address just the biomedical research challenges Matt wrote about.
Today, a study in the Lancet reports on a significant Parkinson’s research breakthrough: the discovery of a biomarker that, for the first time in living people, can detect dysfunction in the protein that goes haywire in Parkinson’s disease. Its advent heralds the arrival of the disease’s biological era. But it’s also an order-of-magnitude leveling up in what Parkinson’s patients can expect out of therapeutic development and, down the line, clinical care. The breakthrough, which comes in the form of a spinal fluid test, was enabled through an effort led by the foundation for more than a decade, the Parkinson’s Progression Markers Initiative. This is a longitudinal, large-scale study pursuing biomarkers of the human disease, sponsored by the foundation (a truly rare role for a nonprofit — these types of large-scale efforts are much more typically sponsored by the government or large pharmaceutical companies).
Scientists on our staff and advisory boards, including those who’ve led the Parkinson’s Progression Markers Initiative since 2010, have been happily stunned by the test’s strength in detecting Parkinson’s at the molecular level, even before any symptoms have shown up — its specificity and sensitivity are off the charts. (Or so the Ph.D.s tell me — this is where I insert my obligatory comment about not being the science guy.) As for me, I can’t stop thinking about how grateful I am to everyone who’s made this happen: the scientists, clinicians, study volunteers, donors. It’s a cast of thousands, and I wish I could shake the hand of every single one.
I’m involved in the work of the foundation in many different ways, but I come to this breakthrough first and foremost as a patient. As someone who has Parkinson’s, up until now, I think I could be forgiven for feeling a little left behind in biology’s century. Going all the way back to 1817, when James Parkinson first described the disease in the scientific literature, it’s been a clinically defined condition. You knew you had it because it was your doctor’s opinion that you had it, after giving you a once-over and deciding where you fell from one to five on a rating scale. (In 2011 a new brain imaging technique allowed us to start visualizing dopamine dysfunction in the brain — another key pathology related to Parkinson’s, but not in itself a measurable biomarker of disease risk and onset.)
This has been at the heart of what our foundation has endeavored to change by patching up what we see as a broken research system. Its holes include an insufficient infrastructure for drug trials, a dearth of clinical research participants, siloed efforts from stakeholders with very different definitions of return on investment — and maybe most of all, the absence of leadership to coordinate existing efforts, leverage great science, and help more people living with disease. At the foundation, we refer to this kind of top-down, streamlined authority as “The Department of Cures,” and — spoiler alert — it doesn’t exist. So we set about doing the journeyman’s work of connecting dots and filling gaps.
The Parkinson’s Progression Markers Initiative is a pretty good example of the foundation-shaped holes we’ve set out to fill. It was born in 2010 after we had fully absorbed the realization that every potential new treatment, no matter how promising, would fail in Phase 3 clinical trials if we didn’t have an objective biomarker to assess its effectiveness. We launched the study with the support of precisely one philanthropic donor, and with the voices of some telling us it would never work. It was expensive, ambitious, and risky, but we thought it was a risk we had to take.
Today the Parkinson’s Progression Markers Initiative is a $500 million effort carried out in partnership with the Aligning Science Across Parkinson’s initiative. It’s supported by about a dozen philanthropic donors, a consortium of 40 biotech and pharmaceutical companies, and tens of thousands of individual donors, and is closing in on 2,000 participants at 51 clinical sites around the globe. Its open-access data sets are downloaded by researchers worldwide on average 2,200 times a day to speed knowledge turns in Parkinson’s biology. The foundation has pounded the pavement to secure every donor, involve every company with a Parkinson’s program, enroll every participant, bring every site online. And now that the study has done precisely what it was built to do — significantly accelerating the validation of a promising biomarker in more than 1,100 Parkinson’s patients, controls and at-risk individuals over the course of less than a year — we are reminded anew how completely worthwhile this work has been.
What does this mean for others working to make biology’s century come true for everyone? Here are a few things we’ve learned along the way:
- Purity of motive matters. We stay true to the only ROI we care about — better treatments (and ultimately, a cure) to benefit everyone with Parkinson’s. Our promise to our partners is that we will behave as people with Parkinson’s would behave in service of accelerating our end goal— seeking opportunity, embracing risk and staying open to new approaches.
- Act boldly. We’re sober about how much work remains on the path to our goal of eradicating Parkinson’s. To get there, we’ll take on anything we need to, even the daunting stuff. By the same token, biology is hard, and much of what we try will fail. When something isn’t working, we stop and look for another direction. We’re problem solvers and we’re optimistic.
- Make the most of the advantage you get from being underestimated. It’s fair to say that when we were starting out, no one expected much from a “celebrity charity.” No matter — we put our heads down and committed to tackle the arduous (or tedious) challenges that other stakeholders wouldn’t or couldn’t. Today, few would deny that we’re moving the needle.
Colossus though it is, the Parkinson’s Progression Markers Initiative is just one of many things we do at the foundation — mostly hard, unglamorous work that rarely makes the pages of STAT. Still, we’ll keep at it until we’ve gotten all the way to the cure for Parkinson’s. Maybe it’s just my perennial optimism, but in the glow of our great leap forward I feel especially positive. Making ourselves ready for biology’s century is hard work, but we can do it. After all, if not us, who?
Michael J. Fox is an award-winning actor, best-selling author, and founder of The Michael J. Fox Foundation for Parkinson’s Research. He was diagnosed with Parkinson’s disease in 1991.
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