The following first appeared on tmrwedition.
Todd Sherer, PhD, is the Chief Executive Officer of The Michael J. Fox Foundation for Parkinson’s Research (MJFF). MJFF is the largest nonprofit funder of Parkinson’s disease research in the world, investing more than $750 million in research to date. Dr. Sherer directs MJFF’s research strategy and is responsible for the organization’s overall scientific and fundraising direction to speed treatment breakthroughs and a cure for Parkinson’s disease.
Dr. Sherer has been a key architect of the Foundation’s strategy to define high-priority research areas for Parkinson’s disease — therapeutic targets and approaches that are closest or most critical to practical relevance in patients’ daily lives — in order to leverage donor-raised capital to push projects in these areas toward the clinic. He has played a major role in the Foundation’s efforts to increase the pharmaceutical industry’s investment in Parkinson’s disease drug development and engage the patient community to encourage and expand participation in clinical research.
Watch a video on The Michael J. Fox Foundation research strategy:
The following has been paraphrased from an interview with Dr. Todd Sherer on January 22, 2018.
(Click here for the full audio version)
How much relative growth would you say the field of Parkinson’s disease research has experienced in the last 5-10 years? Do you believe this pace of growth is accelerating?
I think we are in an upward trajectory in terms of the pace of growth and discoveries happening, particularly in our understanding of what might be causing Parkinson’s. A lot of this has been driven by genetic discoveries made over the last decade, with some trials that have gotten all the way to the clinic. These have also helped us develop a much better understanding of the underlying disease process. We have also seen a number of new drugs approved to treat the symptoms of Parkinson’s disease over the last couple years. We have also seen a lot of new players in academia and in the pharmaceutical industry enter the field of Parkinson’s disease research.
What have been some of the most significant findings so far from the Parkinson’s Progression Markers Initiative (PPMI) study and what do you hope comes of it? (full disclosure, I am a PPMI participant)
One of the things that we are learning from the PPMI study is how varied Parkinson’s is from individual to individual. The only way we can get that information is through the participation of people with Parkinson’s. They are the true experts in this disease, and only through partnering with them can we increase our understanding and ultimately develop effective treatments.
The PPMI study was designed to increase our understanding of the progression of Parkinson’s and to develop markers or objective measures to track that progression. It has been going on for seven to eight years and has made three main pillars of contributions to our understanding of this disease. Some of these are specific scientific findings. We have also established an infrastructure that we can build upon for additional research focused on understanding the cause and progression factors in Parkinson’s, and we have started to see the outcomes of this study influence novel clinical trial design.
Another of its main contributions has been the inclusion of dopamine imaging of the brain in new trials. Many of the symptoms of the disease are due to a loss of dopamine, and we can now use DaT scans to measure the levels of dopamine activity in the brain due to validation in PPMI.
PPMI is also providing an infrastructure for the future of research as all of the data and bio-samples collected are made available to researchers throughout the world for free. We are also seeing more partners building upon that database to accelerate our knowledge of the disease and develop new treatments.
A number of MJFF projects revolve around trying to discover a biomarker for this disease. If we did find a reliable biomarker, what would the next steps be?
One of the biggest challenges we have is how expensive and long clinical trials are to test new treatments that slow the course of the disease. Because the disease progresses so slowly, it takes us a long time to test if therapies are effective. A biomarker, which could come from something like a blood test or a brain scan, could give an objective marker to tell us more quickly if the treatments we are testing are working. This would have an immediate impact on the speed and the cost of clinical trials as it would allow us to test many more treatments and get results faster. It would also make investigating Parkinson’s less risky, which would encourage more companies and people to enter the field.
How would you define the word ‘cure’? How many different ‘cures’ do you suspect we will need to tackle this disease?
In the broadest sense it would mean no one ever gets Parkinson’s disease; we would be able to detect and intervene before anyone ever develops any of the symptoms of the disease.
But we also break it down into several tiers of ‘cure’. There is also the goal of trying to keep people at the stage of disease where they are. Meaning that once someone is diagnosed, could we develop a treatment that keeps someone at that level for the rest of their lives? So we are looking at a balance between trying to treat the symptoms as well as the underlying disease process.
The biggest change over the last five to ten years has been a focus on the different forms of Parkinson’s disease. A lot of this is driven by some of the genetic findings. We are moving more and more towards a ‘precision medicine’ approach, where we will have specific treatments for specific subsets of Parkinson’s. This is already happening for individuals that have GBA and LRRK2 mutations. There may not be one silver bullet for everyone with Parkinson’s, but as we start to better define the disease we can find treatments that help subsets of the population and then try to apply those treatments more broadly.
What do you believe are the most important unsolved questions in PD research today?
What I see as most important is trying to get a better biological understanding of the variability in Parkinson’s. Some specialists say that when you’ve met one person with Parkinson’s, you’ve met one person with Parkinson’s. But we need to move this beyond phenomenology and into understanding by identifying biological subgroups of the disease and then develop very specific biological targets against that subgroup. Also why do some people progress more quickly than others? Why do some people get it earlier than others? And then can we turn that understanding into directed therapies?
If you were starting a career in PD research, which branch would you pursue?
For me one area that has become very exciting is the intersection between technology, data analytics and biology using technology to assess the symptoms of the disease, through wearable sensors or sleep monitors, and through new imaging techniques. We are also developing new content from biological samples, collecting millions and billions of data points from each patient that will need to be analyzed using emerging technologies and state-of-the-art analytics. This is what is going to move the field forward, and it takes a really unique training to develop an expertise in the biology as well as the technology and mathematics, but I think this is a very promising field to go into as a new scientist.
In a quote from Jon Palfreman’s book Brain Storms, Michael J. Fox Says to Deborah Brooks (co-founder of MJFF)… “The last thing I want is for you and I to find ourselves discussing our twentieth annual fundraiser. In fact, if that day ever comes you’re fired.” I believe we are two years away from that date. Is the reason why we haven’t solved this yet because this disease and the brain are more complex than we anticipated, or is it because we are not as smart and/or collaborative as we need to be to solve this?
I think it is a combination. The first thing that is very clear is that not only is the brain more complex than we anticipated, but Parkinson’s disease is also more complex than we thought. I started in PD research about 20 years ago, and the reason I chose Parkinson’s is that I was very interested in doing disease-relevant research in neuroscience. When I looked at different diseases, it seemed like we knew the most about Parkinson’s. At the time it was believed that all the symptoms of PD were due to the loss of a very small percentage of dopamine cells in one region of the brain. I thought, that’s not going to be that hard, if we can just keep 10-20% of those cells from degenerating we’ll cure Parkinson’s. We now know there is much much more to this disease than that and the more we learn about this disease the more we realize that we are not as smart as we thought we were.
But how the research is being conducted is also key. One of the roles MJFF has played since starting is to really incentivize collaboration and bring the industry and academic communities together to work closely in problem solving. We are also doing this by developing studies like the PPMI study, which should have been done 20 or 30 years ago, to establish a better baseline understanding of the disease.
However I do think it is also critical that we promote competition in this field, as well, so that researchers and companies have that incentive to get to the goal line first. We are moving in the right direction, but it is important that we look carefully at how the research is being conducted to ensure collaboration yet at the same time instilling a sense of urgency.
Watch a video on the importance of clinical research participation: