A New Precision Medicine Initiative in Parkinson’s Disease… and Perhaps Other Neurologic Conditions

Brain neuronsCancer was once considered a single disease, but today we are well aware of the many different forms this medical scourge can take, and the many molecular events that can lead to and drive unwanted cell growth. Now, a new partnership between the Michael J. Fox Foundation and 23andMe aims to explore whether Parkinson’s disease is actually a spectrum of different conditions, each driven by its own genetics and perhaps responsive to different treatments.
There are plenty of reasons to support the value of exploring the idea that “Parkinson’s disease” is actually a collection of multiple central nervous system disorders with overlapping sets of symptoms. Some patients only experience movement-related problems, while others suffer cognitive issues. Some go downhill quickly in their health, while others experience only a modest decline. Some patients are affected while still in their 20s, while the disease strikes others when they are in their 70s. And some are affected with tremors, while others develop an abnormal gait. The new research partnership aims to gather sufficient genetic data to segment the disease into different genotypes. This, in turn, could lead to the development of drugs against each of the identified genotypes.
The Michael J. Fox Foundation has already established a substantial data-gathering effort, with over 7,000 adults diagnosed with Parkinson’s disease and their families regularly sharing information about their health and how the disease affects their lives. De-identified data from this ongoing effort, the Fox Insight Study, has been shared with the research community and has helped to better understand the needs of patients, redefine therapeutic priorities, and optimize clinical trial designs.
The partnership with 23andMe, called FIGS (Fox Genetic Sub-study), adds a genotypic component to this research. By sending out 23andMe spit kits to gather saliva samples that will be analyzed for possible genetic variants, FIGS will try to understand the ways in which Parkinson’s disease in one patient differs from the disease in others. The number of samples gathered is a critical factor, and 23andMe has already enlisted more than 12,000 patients with Parkinson’s disease since 2009 for its own research, which will be added to the effort. The partnership ultimately hopes to collect data on tens to hundreds of thousands of patients, which will be made available in de-identified form to independent scientists for study. Any discoveries made using the data, including new drugs, will be patentable by their discoverers, but Fox and 23andMe will receive a non-exclusive license.
There are some limitations to the effort as it has been announced. A critical factor for the success of this partnership will be the clinical accuracy with which participants are assessed, as this will be key to defining clinically distinct disease segments. Additionally, much more data – both in terms of sequencing and numbers of patients contributing to the effort – will likely be required for the most comprehensive view of variants associated with different types of Parkinson’s and the identification of useful biomarkers to help guide drug discovery, development, and clinical usage.
And what would be the consequence of identifying a genotype that only affects 1-2 percent of Parkinson’s patients? Would the pharma industry even pursue drug development against such a genotype, as it would move the disease to an orphan – if not ultra-orphan  – designation? Could the cost of drug development – or the cost of an ultimate therapeutic – be supported by either the industry or payers?
Additionally, will this new approach to Parkinson’s disease be extended to other CNS conditions, such as Alzheimer’s and epilepsy? Research is increasingly revealing that there are previously unrelated genes that show similar disease phenotypes. Perhaps as large databases of phenotypic and genotypic data related to neurological conditions are assembled, they will lead to a variety of new CNS disease hypotheses and drug development strategies for such illnesses.