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STAT: 'Michael J. Fox Foundation partners with 23andMe for precision medicine project on Parkinson's'

STAT: 'Michael J. Fox Foundation partners with 23andMe for precision medicine project on Parkinson's'

Today, STAT covered the launch of Fox Insight and the collaboration between The Michael J. Fox Foundation and genetics testing company 23andMe to advance the study of Parkinson's genetics. The story includes interviews with Todd Sherer, PhD, MJFF CEO, and Anne Wojcicki, 23andMe CEO and co-founder.

Read the full piece below.

Michael J. Fox Foundation partners with 23andMe for precision medicine project on Parkinson's
October 30, 2017
By Sharon Begley

First cancer. Now, Parkinson's?

The idea that one disease is actually several, each driven by its own genetics and differing in everything from age of onset to response to drugs, made cancer the poster child for precision medicine. Now, a $4 million study announced on Monday aims to see whether a genetically informed precision-medicine approach might work for Parkinson's, too.

The study is a partnership between the Michael J. Fox Foundation for Parkinson's Research and the genetic testing company 23andMe. One goal: to identify new drug candidates.

Since 2015 some 7,000 adults worldwide have been contributing to the foundation's online "Fox Insight" study. So far the data have been about patients' "lived experience," said foundation CEO Todd Sherer: via questionnaires every 90 days, they describe their symptoms and experience with medications, for instance.

But through the partnership with 23andMe,"FIGS" (the Fox Insight Genetic Sub-study) -- which starts enrolling volunteers immediately -- will add a genetic component. Patients will use 23andMe's spit kit to send the company biological samples that will be analyzed for possible genetic explanations of the many ways Parkinson's disease in one patient is different from Parkinson's in another.

DNA variants might show, for instance, why Parkinson's, which affects some 1 million people in the U.S., causes only movement problems in some but also cognitive decline in others; why some patients go downhill fast but others hardly decline; why it strikes some people in their 20s but others in their 70s.

"I think it could be very, very useful to break the disease apart into genotypes and try to develop drugs against each," said medical geneticist Matt Ferrer of the University of British Columbia, a leading expert on the genetics of Parkinson's who is not involved in the new project. Medically, "it's much better to be precise, getting the right drug to the right patient" as oncologists do in, say, lung cancer, he said.

Even if that succeeds scientifically, however, there might be commercial hurdles.

"Big drug companies want to sell blockbusters, to as many patients as they possibly can, not develop different drugs for every subtype of Parkinson's," said Ferrer, who has received research funding from the Fox foundation. "It all comes down to economics: Will a company invest in R&D if something will serve only 1 or 2 percent of the Parkinson's population? I think we're years away from drug companies wanting to segment the Parkinson's market."

The Fox foundation and 23andMe are more optimistic. Even before genetic data offer up possible drug targets for different subtypes of Parkinson's, it might show why patients differ in how quickly they decline, the severity of their movement symptoms, whether or not they also suffer cognitive problems, and whether their main movement symptom is tremor or a abnormal gait.

That could give people who undergo genetic testing and learn they have a Parkinson's-associated DNA variant a better idea of what they might be in for. "People want to understand their pathway," said 23andMe CEO and co-founder Anne Wojcicki.

But she is also determined "that new, novel therapeutics will come out of this,"Wojcicki said, including drugs to target subpopulations of Parkinson's patients based on their genetics.

"One of the hopes we have here is that every disease is starting to have subsets," she said. "You can do that with cancer, and I think that will happen more and more with Parkinson's, with different [genetic] pathways receiving different treatment."

Some 70 genes associated with Parkinson's have been identified, said UBC's Ferrer, including LRRK2, PARK7, PINK1, and PRKN. But few explain the dramatically different courses it can take.

One key to success will be scale, said geneticist Daniel MacArthur of the Broad Institute of MIT and Harvard, an expert on using large datasets to identify DNA variants linked to disease. "The number of samples will be crucial," he said. "But 23andMe"-- which has enlisted 12,000 Parkinson's patients since 2009 for its own research on the disease -- "has already shown that it has a fantastic ability to recruit people."

Also crucial, said MacArthur, who is not involved in this project but has collaborated with 23andMe on other research, is high precision and accuracy in describing individual cases. Otherwise genetic correlations with different subtypes will be at best muddled, and at worst meaningless. The study would also likely produce more, and more useful, results if it sequenced patients' genome (or at least their exomes, the protein-coding part of the genome), MacArthur said. But 23andme will do only genotyping, or analyzing DNA for known genetic variants, not sequencing, which means useful genetic data could be overlooked.

FIGS will collect data via online surveys as well as objective measures such as how quickly and accurately people can type on a keyboard, and wearables that capture data on gait and tremor. It is not yet clear how precise and accurate those data, especially the self-reported parts, will be.

The Fox foundation has spent $6 million so far on the Fox Insight study, and will pay 23andMe $4 million to conduct the genetic sub-study, including to make the spit kits and DNA analysis free to study participants.

Starting next year, de-identified data from Fox Insight will be made accessible to independent scientists, the foundation said, in hopes of accelerating understanding of Parkinson's and the development of better drugs to treat it. Scientists who use the FIGS data will be allowed to patent any discoveries they make, including of new drugs, but will be required to provide both the Fox foundation and 23andme non-exclusive licenses to it.

Assuming FIGS does identify new drug possibilities specific to one subtype of Parkinson's, 23andMe and the Fox foundation would have their work cut out for them.

"Every time I go to a drug company after we identify a mutation" that causes only some cases of Parkinson's, UBC's Ferrer said, "I'm asked, 'might this apply to the whole population of Parkinson's patients?'"

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