Genentech Strikes Deal with 23andMe to Study Parkinson’s Genomes

In trouble with the FDA, the personal genomics company 23andMe stopped sharing genotype information with its customers back in 2013, but by then it had already amassed a fortune in genetic gold. Now that treasure trove of DNA is paying off, and Parkinson’s patients stand to benefit. On January 6, the Mountain View, California, company signed a deal with Genentech to share genomic and phenotypic data from 12,000 volunteers who have PD. Genentech will give 23andMe $10 million up front and another $50 million down the road to finance the collaboration. The two companies aim to sequence the entire genomes of 3,000 PD patients, with their consent. They hope the data, which will be made available to the rest of the research community after two years, will yield new targets for drug discovery and diagnostics.

“We strongly believe the best way to find new therapeutics is to fully understand the biology of disease, and genetics is a critical part of this,” said Alexander Schuth of Genentech. Rich clinical information greatly enhances 23andMe’s sizable collection of genotyped DNA samples from Parkinson’s patients, making the database ripe for fruitful exploration, Schuth added. Typically with GWAS and genetic sequencing samples, the lack of detailed phenotypic descriptions of the people contributing the blood sample limits the interpretation of genetic results.

The Parkinson’s community within 23andMe has been in the making ever since CEO and co-founder Anne Wojcicki’s husband, Google founder Sergey Brin, used the company’s kit to find out he carries an autosomal-dominant mutation in the LRRK2 gene. The variant puts Brin at risk for PD, a disease his mother has. In 2009, 23andMe launched a campaign to invite PD patients to send in their saliva for analysis—free of charge—to build a genetic database. Prior to 2013, patients received genotype profiles in return, which told them whether they carried LRRK2 mutations or other variations related to PD, just like customers who purchased DNA analyses from 23andMe. In 2013, 23andMe ran afoul of the Food and Drug Administration, which was concerned that proper steps were never taken to have the company’s diagnostic tests approved, and subsequently 23andMe only provided customers and patients with ancestry information and raw data (see Feb 2014 news). Savvy customers can still use the latter to figure out their genotype with the aid of gene ID numbers and online databases.

The company spread the word about its PD campaign with the help of advocacy groups such as the Michael J. Fox Foundation (MJFF), the Parkinson’s Institute, and the National Parkinson’s Foundation, as well as through clinicians, social media, and conferences. After 3½ years, 10,000 PD patients had signed on, said Emily Conley, 23andMe’s director of business development. The company’s PD community has since reached 12,000, and continues to grow.

Many of 23andMe’s PD patients were recruited through MJFF’s Fox Trial Finder, Conley said. The Web tool matches willing PD patients, family members, and friends with clinical studies all over the world. While some patients do not qualify for trials due to their location, disease stage, medications, or other criteria, everyone qualifies for the 23andMe study. MJFF helped 23andMe design a detailed, PD-centric questionnaire that went far beyond that filled out by the typical 23andMe customer. Participants supplied information about their family history, disease stage, age at symptom onset, symptom severity and progression, medications taken and which ones helped, history of pesticide exposure or head trauma, caffeine intake, and so on. “This deeper phenotypic questionnaire makes the genetic data that much more valuable,” said MJFF CEO Todd Sherer.

Genentech was one of 23andMe’s original investors and has collaborated with the company before. The biotech company, now a part of Roche, wanted to explore this rich genetic resource in the hope of finding new therapeutic targets via whole-genome sequencing. Genentech will seek additional consent from participants to fully sequence their genomes and study their de-identified data on an individual level. Those 23andMe customers who opt to participate in research normally consent to share data only in the aggregate. Viewing both the phenotype and genotype data on an individual level will allow Genentech to select the best cohort for whole-genome sequencing, Conley said, because its researchers will be able to make sure to include a representative sampling of patients with different disease characteristics or known genetic mutations. She expects many patients to come aboard, especially since all of them signed up with the intention of furthering PD research. The researchers aim to sequence 3,000 PD patient genomes.

What will they do with all that data? According to Schuth, the major goal is to identify genetic factors that cause or influence disease. Schuth believes these can be found in regions of the genome previously untouched by exome sequencing or GWAS, such as the one 23andMe already conducted on a subset of its PD cohort in 2011 (see Jul 2011 news). The phenotype data will also allow the researchers to identify genetic variants that hasten or slow disease onset, speed up or slow down progression, or protect some people from developing the disease at all. Genentech also plans to enroll some of the 1,300 healthy relatives of PD patients who have signed on with 23andMe.

Conley said the researchers are looking for rare variants that have strong effects. “Though we might find genetic variants that only occur in one or two people out of the 3,000, they might explain some mechanism of the disease that wasn’t understood before,” she said. “This could help us develop a treatment that can be used for everybody.”

Schuth said another major goal is to develop diagnostics that will help researchers gauge which patients are most likely respond to a given treatment.

“The 23andMe experiment has been a very interesting one,” commented Mark Cookson of the National Institutes of Health in Bethesda, Maryland. “It’s been an efficient way to motivate people to do large-scale genetic studies.” The cost of whole-genome sequencing and the infrastructure needed to analyze the data places an undertaking like Genentech’s out of reach for many academic institutions. While it is difficult to tell if 3,000 patient genomes will be sufficient to find important variants, the only way to know is to try, Cookson said.

In addition to its collaboration with Genentech, 23andMe signed more than a dozen deals with other pharmaceutical companies in 2014, Conley said. She declined to give details but said some will focus on other neurodegenerative diseases, such as Alzheimer’s. However, she said that the company will only study aggregated genotype data in those partnerships, rather than launching into full-fledged individualized genome sequencing. On January 12, the company announced it would share genotype data from 650,000 of its 800,000-person database with Pfizer (see Bloomberg news).

Asked whether this rash of pharma partnerships reflects a change in 23andMe’s business model, Conley gave a resounding “no.” “One of the big misconceptions out there is that this is a big shift for us,” she said. “This was a big part of the vision when the company was founded almost nine years ago.”

To those who have concerns about the company selling genetic data to pharmaceutical companies, Conley pointed out that all participants have given consent for such sharing, and that partnering with companies such as Genentech is the best way to advance the development of therapies. “People are volunteering their information, and they’re excited that we’re actually using it in a meaningful way,” she said.

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