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Navigating the 'Many Roads to Rome': MJFF Partner 23andMe Drives Genetic Research Toward Drugs to Treat Parkinson's Disease

Navigating the 'Many Roads to Rome': MJFF Partner 23andMe Drives Genetic Research Toward Drugs to Treat Parkinson's Disease

In spring 2009, personal genetics company 23andMe announced that it would recruit 10,000 people with Parkinson’s to contribute DNA for research to illuminate the role of genetics in PD. Three years later, 7,500 people with Parkinson’s across 49 U.S. states and 26 countries have joined what has become the largest Parkinson’s community for genetic research worldwide.  23andMe researchers are making progress toward building a greater picture of the underlying causes of the disease, genetic and otherwise.

“23andMe’s unique initiative leveraging DNA technology, the Internet, and patient participation is already enhancing understanding of Parkinson’s disease,” says Todd Sherer, PhD, CEO of The Michael J. Fox Foundation (MJFF). “Ongoing results could open new approaches to developing drugs.”

There are many reasons for conducting genetic studies tied to PD. One is to better predict an individual’s risk for developing the disease in the long-term. Another reason is that, by studying genetic mutations, researchers hope to better understand the molecular processes taking place during the course of PD, in both genetic and sporadic cases of the disease. This could lead to improved drugs to counteract these processes.

MJFF has been a publicity partner to the PD Research Community, helping spread the word to people with Parkinson’s about the opportunity to speed research progress by mailing in a saliva sample to 23andMe to collect the DNA it needs to analyze people’s genetics.

Today, Sherer, Michael J. Fox, and Foundation Co-Founder Debi Brooks are visiting 23andMe’s Mountain View, California offices to see the operation first hand.

“The Foundation has played a major role in research progress we’ve made to this point,” says Emily Drabant, PhD, Research Development Manager at 23andMe. “Today’s visit gives us the chance to share updates with Todd, Michael, and Debi personally — and think through opportunities to continue our fruitful collaboration.”

Read on to learn more about some of 23andMe’s advances in research.

Bigger, Faster, and More EfficientAnne Wojcicki established 23andMe in 2006. One of the first to be genotyped by the company was her husband, Google co-founder Sergey Brin. Brin learned that he had a mutation in a gene called LRRK2, the greatest genetic contributor to Parkinson’s discovered to date.  (Brin’s mother Eugenia also has PD.)  In response to this knowledge, Brin told Wired magazine that he decided to make significant lifestyle changes to exercise more and change his diet in an effort to limit his risk of one day developing the disease. He also decided to underwrite the participation of people with Parkinson’s in 23andMe to enable a special PD initiative.

“We can make significant progress in understanding Parkinson's disease if individuals join together and contribute their personal experiences to scientific research,” Brin said at the time. “Individually, our genes and experiences are lost in a sea of statistical noise. But, taken together they become a high-power lens on our inner workings.”

“When we launched this initiative, we were extremely frustrated with the slow pace of research progress; with how expensive and how long it takes to recruit for clinical trials,” says Drabant. “So we thought, why not bring people together on the Internet to do Parkinson’s research bigger, faster, and more efficiently than ever before?”

In addition to sending in their saliva samples, participants answer surveys online about their experience with PD.  Data is then analyzed and results are made available to the research community at large.

All members of the PD community are entitled to free lifetime memberships to 23andMe, and receive detailed, personalized reports indefinitely through the 23andMe Personal Genome Service™.  They also can share their experiences directly with others in the online community.

Proving the Model Works

“When we first put out the idea that we should recruit on the Internet, many neurologists said that our model would never work,” says Drabant. “That we wouldn’t be able to recruit on the Internet, and that even if we did, people wouldn’t report accurately on their experience with PD.”  Without a clinician to guide patients, many thought, data would become skewed.

Within two years, the company had replicated 20 genetic mutations already known to scientists, while also contributing new genetic mutations. By combining genetic testing with online reporting, 23andMe had come to similar conclusions as researchers collecting in a traditional clinical setting. It was a critical proof point for the company’s methodology.

Many Roads Lead to Rome

Positive data in hand, 23andMe has continued to move forward to tackle increasingly complex questions about PD, and the role that genetics might play in the onset of the disease. Today the company is announcing the addition of five new genetic variants related to PD to their Parkinson’s report, bringing the total since inception to 10. Participants in the Parkinson’s community can view their personal genetic results for all 10 variants inside their 23andMe profile.

“In the search for causes of PD, it’s increasingly clear that many roads lead to Rome,” says Drabant. “If we can better understand what each of these roads look like, we may be able to better develop treatments to stop the disease.”

Last November, 23andMe researchers found that a form of a gene called SGK1 appeared to protect people from the higher risk of PD conferred by mutation in LRRK2. In work funded by MJFF, The Scripps Research Institute will further investigate the relationship between SGK1 and LRRK2, and whether SGK1’s action could lead to a druggable Parkinson’s target.

Strength in Numbers

Anne Wojcicki has likened genetic discovery to locating a needle in a haystack. But the more chances you get, the more likely you are to find the needle that may lead to a critical scientific discovery. The more people who sign up for a particular genetic study, the greater the study’s power.

Most progress in genomics has been made through large-scale studies of familial populations with similar genetics: By analyzing large pools of similar data, researchers can home in on shared characteristics that play a role in disease. Much of 23andMe’s success has been based in their ability to recruit large numbers of people with PD, fast.

Of course, the decision to have one’s genome tested is a nontrivial and personal one that impacts not only the individual but the entire family. Given our current understanding of PD, knowing genetic risk likely won’t inform an individual’s life choices, and there's no current action plan for preventing PD or treating it differently based on the DNA card you’ve been dealt.

Still, taking part in genetic research, especially families with a history of Parkinson’s, can be critical to speeding new and better treatments for the disease. Whether it’s by finding out your genetic make-up directly through 23andMe, or signing up for more traditional genetic research studies where learning your gene status is not required, your participation can help move the field forward.

To learn more about how to get involved in ongoing PD genetic studies, create a profile at Fox Trial Finder, the Foundation’s clinical trial matching tool. And if you know your genetic status, be sure to answer the question about genetic testing.

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