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Is Parkinson’s Disease Ready for Precision Medicine?

December 1, 2016
by Rajiv Leventhal
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In an editorial this summer published in Personalized Medicine, authors from The Michael J. Fox Foundation for Parkinson’s Research and J. William Langston, M.D., chief scientific officer and founder of The Parkinson’s Institute, outlined a strategy to advance precision medicine in Parkinson’s disease (PD). Lead author Todd Sherer, Ph.D., CEO of The Michael J. Fox Foundation and his co-authors believe that by pivoting from traditional definitions of disease to profile pathology by genetic and molecular changes, neurodegeneration researchers can design and test more targeted therapies with higher likelihood of success.

But challenges do remain, as precision medicine approaches are still immature in most areas of care, with PD being no exception to that. “Truly transforming PD treatment into a precision approach will require tackling key research and regulatory challenges, and the coordinated effort of the entire PD community,” the authors wrote in the editorial. “With our growing understanding of the varied paths to Parkinson’s disease, we see potential routes to personalized medicine for our field,” added Sherer. “Increased attention and collaboration in this area will mean significant advancement in the identification and testing of new treatments to prevent, slow or stop disease.”

Todd Sherer, Ph.D.

Sherer, a key architect of the foundation's strategy to define high-priority research areas for Parkinson's disease, spoke further to Healthcare Informatics about the potential of precision medicine to be effective for PD, where the challenges lie, and what the impact could eventually be. Below are excerpts of that discussion.

What should we know about the latest in Parkinson’s disease research?

There is a lot of excitement right now in Parkinson’s disease research and the conversion of that research into potentially new treatments for PD. Right now, the disease is a progressive neurological disease, and while there are some treatments for the motor symptoms, there has been nothing that targets the underlying disease process in a way that a treatment that can slow the disease. That’s what’s been missing. The challenge we have had is a lack understanding of what might be the causal factors. What molecular processes and genetic factors might be leading to the disease? To develop a drug to slow this disease, you might want to target what’s actually causing cells in the brain to die.

The exciting new advance in the last five years or so is an increase, understanding, and identification of what these causal factors for the disease could be, particularly coming out of some important genetic discoveries or molecular discoveries that can lead to PD. Some of that understanding has been converted to therapies that are being tested in clinical trials. So for the first time, we have a robust pipeline of treatments that could potentially slow the disease.

There are plenty of strong examples of precision medicine in oncology. How can this approach be applied similarly to PD?

Historically, we have known there is a great variability in the symptoms of people who have PD and also a great variability in the people who have the disease, in terms of age, cause of disease, family history, how quickly it might progress, and how they respond to medicine. There has always been a great clinical variability. Now, we have the first indications of being able to better segment and understand this patient population based on the biology and the ability of genetic factors to contribute to the disease. This is leading to a re-definition of how we’re thinking about PD where we have the potential to subset the disease by the underlying biology, which is similar to the oncology example, which is now identified and characterized by certain molecular changes, [allowing] you to develop treatments to target those molecular changes.

We are not there yet for PD in terms of having the targeted therapies, but we are gaining information to better understand the segmentation of the population and how the underlying biology could be continuing to the various expressions of the disease and ultimately have the potential to develop targeted treatments. It’s important to think about PD through this lens, we have a much greater chance of success, as has been demonstrated in oncology, if we can develop the right treatments for the right patients at the right stages of their disease rather than lumping all PD patients together. If you do that, you might lose evidence for an effective therapy since it might only be effective for a subset of the population.

What other gaps need to be filled in order for precision medicine to be effective for PD?

We need to increase our understanding of the molecular contributions to the disease and how the different molecular pathways link to the actual clinical symptomologies of the disease. We don’t have that good direct link between genetic factors, the onset of disease, the progression of disease, and how those genetic factors could impact biological pathways that we can intervene with. We are in the early days of converting this perspective of PD into our ability to develop those types of therapies. We have to do a great amount of research and we have to understand the progression of the disease and the impact of the biological disease on that progression.


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