Precision Medicine
Regina Kelder

Precision Medicine

The world of Big Data and genetic testing are upon us. Are patients ready for it? A report from the Harvard meeting.

Precision medicine could dramatically change—the Obama administration says revolutionize—how we prevent, diagnose and treat diseases large and small. But are we truly ready to embrace it?

Scientists from a few key disciplines—bioinformatics and geneticists being two of the biggies—are discussing and debating how to bring precision medicine to the bench and to the bedside. And parents of children with rare diseases are perhaps the biggest advocates of precision medicine, which, loosely speaking, tailors treatments based on an individual’s characteristics.

But the general public probably couldn’t tell you what precision medicine actually means or why they should care about it. Even doctors have a hard time understanding how to use precision medicine or how to apply it to their practices.

Karen Aiach, founder and CEO of French-based Lysogene, understands the concept, though. The former financial consultant founded the gene therapy biotech seven years ago to find a treatment for her daughter, Ornella, who was diagnosed at 6 months of age with a rare inherited lysosomal storage disorder called Sanfilippo syndrome that causes widespread cognitive dysfunction and kills its victims by adolescence.

“We needed to do something,” said Aiach during her moving keynote address at Precision Medicine 2016: Rogue Therapeutics, a June 22 conference hosted by Harvard Medical School. “It was our duty as parents not to abandon our child … to find a cure for that disease. Whatever it took, I had to find my way.”

Lysogene’s gene therapy candidate rAAV7, which uses an adeno-associated virus (AAV) vector to deliver DNA directly to the brain, was tested three years ago in a small Phase I/II study of four children with the most severe form of Sanfilippo.  The AAV vector encoding for two genes that help normalize the accumulation of polysaccharides responsible for many of Sanfilippo’s neurological symptoms, was administered directly into the brain matter by drilling six burr holes in the skull. This process is known as intraparenchymal delivery.

The findings, published in Human Gene Therapy, showed no serious adverse effects and some moderate improvement in behavior, attention and sleep disorders. Lysogene is now planning a Phase III trial of rAAV7.

There was a time when it might have been all but impossible to dig into the weeds and find therapeutic solutions for children like Sanfilippo, which occurs just once in every 70,000 live births. But the ability to tease out trends and traits by rapidly analyzing extremely large data sets and the growing availability of whole-genome sequencing, including whole-exome sequencing, to characterize disease variants has made it possible to apply precision medicine, not just to rare diseases but to common ones, too.

 “I want the country that eliminated polio and mapped the human genome to lead a new era of medicine — one that delivers the right treatment at the right time,” the US President Barack Obama said when he unveiled his US $215 million Precision Medicine Initiative last year during a State of the Union address.

The main steps of the White House initiative include analyzing as many cancer genomes as possible to identify genetic factors that lead to cancer, apply the proper level of scrutiny to the burgeoning and increasingly affordable field of genetic testing and to conduct a million-person study of biological and behavioral data that can be used to assess disease risk and understand disease mechanisms.

Matt Might, who successfully mined social media—particularly Google—to find the handful of patients like his son, Bertrand with an extremely rare inherited disorder known as N -glycanase 1 (NGLY-1) deficiency, says data is the key. Might, a White House strategist whose primary focus is on the Precision Medicine Initiative, believes that at the end of the day, “the greatest drug of the 21st century” will end up being Big Data.

But while using genetic tools to find solutions for rare incurable diseases has become increasingly popular—the orphan drug development pipeline is attracting more pharmaceutical investors, for instance—applying the tools of precision medicine to the general population hasn’t been as easy. The clinical utility of rapid, lower-cost whole-genome sequencing is still unproven while combining pre-diagnostic tests with targeted therapies—namely cancer—is expensive and still in in the early stages, noted a group of international scholars last year in the Journal of Law and the Biosciences.

Nor is it clear what business models precision medicine should adopt, how comfortable people are about sharing their genetic data, who will pay for the tests and what the rationale for diagnostic screening is if you don’t also have effective therapies to treat the diseases that these tests uncover.

Gail Marcus, Program Director for Global Health at the Massachusetts College of Pharmacy and Health Sciences in Boston, has viewed the precision medicine landscape as both a provider and a patient. While she was a CEO of a laboratory that did molecular tests for cancer, Marcus was diagnosed with Stage II breast cancer. She was given the Oncotype DX test, an early precision medicine test that measures the activity of genes that control cell growth and uses the information to predict how well a patient will respond to certain treatments. Marcus, an Ashkenazi Jew, was also tested to see if she carried mutations in the tumor suppressor genes BRCA1 and BRCA2 that occur with greater frequency in this ethnic population. She was negative for both.

Marcus asked a lot of questions about her condition, but one question she didn’t ask, even though she also worked on the payer side, was whether insurance would pay for the genetic tests.  “This is one of the biggest challenges patients face,” said Marcus during a panel discussion at last week’s Harvard meeting.  “I was fortunate that my insurance covered it, but that is not always true for a lot of the tests. So part of the dilemma is not just a patient understanding what tests are going to be applicable, but understanding the complexity of our health care system and who is going to end up paying for the tests.”

Carey Goldberg, a health and science reporter at Boston’s NPR station WBUR and joined Marcus in the panel discussion, says reaction to the Precision Medicine Initiative has been tepid compared to the enthusiasm surrounding other White House projects like the National Cancer Moonshot Initiative or the BRAIN Initiative. “There is a disconnect between the rare disease community, which is hugely invested in precision medicine, and the broader public.”

Citing a recent poll conducted by STAT, an online science news site produced by the Boston Globe, Goldberg said that only 50% of Americans have heard or read about genetic testing and only 6% have undergone it. “The clinical benefits to the public are not clear yet, and so there is a high level of indifference,” said Goldberg.

How to Cite:

McEnery, Regina. Precision Medicine. Eureka blog. June 27, 2016.