How 23andMe's Genetic Database Bridges the Gap in Alzheimer Research

While leading genealogy reporting companies continue to amass valuable stores of genetic data from individuals looking to learn more about their ancestral background, pharmaceutical companies have found a new way to utilize these genetic profiles.

For pharmaceutical companies, these massive databases are a veritable goldmine for the research and development of novel therapies for difficult-to-treat neurological conditions. But the question remains of how 2 major entities would share such a mine.

Last month, GlaxoSmithKline [GSK] announced a four-year collaboration with the popular direct-to-consumer genetic testing company 23andMe to research and develop therapies and potential cures for various hard-to-treat conditions.

The collaboration will focus on a variety of research and development initiatives, including improving target selection to allow for safer and more effective precision medications to be developed—supporting the identification of patient subgroups that are more likely to respond to certain targeted treatments, and allow for more effective identification and recruitment of patients for clinical studies.

“We are excited about this unique collaboration as we know that drug targets with genetic validation have a significantly higher chance of ultimately demonstrating benefit for patients and becoming medicines,” Hal Barron, MD, GSK chief scientific officer and president of R&D, said in a statement.

“Partnering with 23andMe, an organization whose vision and capabilities are transforming the understanding of how genes influence health, will help to shift our research and development organization to be ‘driven by genetics,’ and increase the impact GSK can have on patients.”

23andMe offers customers far more than a snapshot of their ancestral composition. Customers can opt to receive a comprehensive analysis of how their genetics can influence their risk for certain diseases, learn how their genes contribute to their well-being and lifestyle choices, whether they area carrier for certain inherited conditions and how their DNA influences their facial features, sense of smell and other genetic traits.

In collecting and documenting this data, 23andMe—and similar companies—have created a massive database consisting of millions of valuable genetic profiles. To hear 23andMe co-founder Ann Wojcicki explain the collaboration, it’s a simple next-step decision.

“By leveraging the genetic and phenotypic information provided by consenting 23andMe customers and combining it with GSK’s incredible expertise and resources in drug discovery, we believe we can more quickly make treating and curing diseases a reality,” Wojcicki said in a statement.

Such collaborations are not unheard of within the pharmaceutical industry. In 2012, Amgen acquired Iceland-based deCODE genetics to utilize its genetic database. That same year, Regeneron Pharmaceuticals partnered with Geisinger Health and Biobank in a similar collaboration.

In 2015, the genealogy company Ancestry launched its personal genetics branch, AncestryDNA and partnered with Google-owned biotechnology company Calico to develop methods to fight aging.

"Our common experience suggests that there may be hereditary factors underlying longevity, but finding the genes responsible using standard techniques has proven elusive," David Botstein, Calico's Chief Scientific Officer and member of the US National Academy of Sciences, said at the time. "This is an extraordinary opportunity to address a fundamental unanswered question in longevity research using high quality human pedigrees."

With millions of customers, companies like 23andMe and AncestryDNA offer vast databases from which to study genetic data and seemingly unbound potential for developing therapies for uncured or difficult to treat conditions, such as Parkinsons Disease (PD) or Alzheimers Disease (AD).

In his own assessment of the to-be-told role 23andMe will play in treating neurological conditions, Gregory Day, MD, MSc, assistant professor of neurology at the Washington University School of Medicine Knight Alzheimer Disease Research Center, told MD Mag that the genealogy company collects and processes tissue samples, providing reports on a limited set of relatively common genes and variants.

“One of these includes APOE allele status,” Day said. “APOE4 allele carriers are known to be at an increased risk of developing symptomatic Alzheimer disease; and this information is communicated to the client.”

However, the true value of that data and therefor the potential for the development of new treatments relies on the accuracy of that data.

“While it’s exciting to see this partnership, and while I acknowledge the great potential for improving our understanding of disease and development of therapeutics, I’ll caution that the connections that 23andMe and GSK are able to forge through this collaboration will depend upon the quality of their self-reported data,” Day said.

In addition to submitting a DNA sample, 23AndMe also asks customers to complete an extensive survey. Due to the self-reporting nature of this portion of the process, the door is left open for inaccuracies, which could result in skewed data.

The most effective and ethical way companies like 23AndMe can contribute to the development of therapies for hard-to-treat diseases such as AD—Day’s area of expertise —would be by partnering with companies or academic institutions “who are actively recruiting participants into longitudinal studies of evaluating the factors that contribute to changes in memory and thinking…or developing and testing medications and /or other forms of treatment that are meant to prevent Alzheimer’s disease in at-risk individuals.”

Enrolling at-risk patients in longitudinal memory and thinking studies is central to understanding the early stages of Alzheimer’s Disease. It is with this information that has helped developers already create imaging and spinal fluid testing that allows researchers to recognize AD-based changes in patients well before they even develop symptoms of dementia, Day noted.

Day added that enrolling at-risk patients in clinical trials for preventative therapies is also essential to the process of developing therapies to treat AD, as they evaluate the effects of medications or lifestyle adjustments in preventing the development of dementia.

“Currently there are several clinical trials doing just that,” Day said. “There are other studies that specifically wish to enroll individuals who have 2 copies of the APOE4 allele. These individuals are at a much higher risk of developing AD.”

However, the rarity of this patient subpopulation makes them difficult to identify, Day said, requiring drug companies screen thousands of patients at a time. The biggest role 23andMe could play is in facilitating clients to the drug companies.

“Such a partnership would potentially allow 23andMe to share information from relevant, vetted institutions [or] companies concerning available opportunities [or] treatment trials with their clients who screen positive for gene variants associated with an increased risk of (AD),” Day said. “This could be done without violating the trust of the client—no client information would be shared with corporations or academic institutions—and would have the added benefit of providing their clients with options that they could then choose to act on should they wish to learn more about active research into these areas.”

The ethics of utilizing data from a genetic reporting company like 23andMe or Ancestry is often called into question due to the fact that customers are not compensated for the use of their genetic data in the research and development of treatments.

However, in the case of 23andMe, customers can choose whether or not to participate in research. Additionally, GSK has stated that customers who do choose to participate in research have identifying information removed from their data.

So as long as the right clients are made aware that customized information regarding study recruitment and research opportunity could reach them—and that they retain the right to opt out of such offers—Day sees no major ethical dilemmas.

Of 23andMe’s nearly 5 million customers, approximately 80% have consented to participating in research, providing for a sizeable data pool. And on average, 1 client has contributed to approximately 200 different research studies, according to 23andMe. There’s wonder if those numbers will grow.

“If done well, and if done ethically, this (collaboration) could be a win for their clients, a win for researchers, a win for society in general,” Day said, “and even a win for their shareholders.”

For more extensive coverage from the Alzheimer’s disease space, check out MD Magazine's sister site, NeurologyLive. The Clinical Focus page serves as a resource for clinical news, articles, videos, and newly released data pertaining to dementia, too.