A close-up view of disease opens pipelines that could carry already-proven medications to new patients.
Precision medicine can be thought of as a science of small details. Investigators are examining individual gene mutations, mapping molecular pathways inside cells, and deciphering diseases one subgroup of patients at a time. For instance, the discovery that mutations in the BRCA1 and BRCA2 genes can cause breast cancer was hugely beneficial for the 5 percent of women who carry those mutations.
It might sound like precision medicine is building silos when it should be breaking them down. Actually, by taking the microscopic view, it’s helping medicine draw a bigger, clearer picture of disease than ever before. It’s also opening pipelines that could carry already-proven medications to new patients.
“If you become agnostic about the organ involved and you become more interested in the underlying causes of diseases, you can start to subtype them by genetic infrastructure,” says Dermot McGovern, MD, PhD, who directs Cedars-Sinai Precision Health as well as Translational Medicine at the medical center’s F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. “We are witnessing the emergence of a new molecular taxonomy of diseases instead of the traditional nomenclature based on particular organs and systems.”
“If I find a genetic signature for a group of patients, and I find a therapy that works for them, then I can look for similar signatures in other diseases — and help more patients.”
— Dermot McGovern, MD, PhD
McGovern — the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics — is conducting inventive research with colleague Michael Weisman, MD, director of Rheumatology and the Cedars-Sinai Chair in Rheumatology.
A decade ago, a gut physician and a joint specialist would not have found common ground in the laboratory. Now they know that many immune-mediated diseases share a genetic architecture, with a particular connection between Crohn’s disease, a form of inflammatory bowel disease (IBD), and ankylosing spondylitis, an inflammatory spine disorder.
“It turns out that there are people with Crohn’s disease whose genetics look much more like some people with ankylosing spondylitis than they do like other people with Crohn’s, and vice versa,” McGovern says. And some patients have both diseases without realizing it. The physicians are discovering treatments that can benefit both groups of their patients and also, importantly, some therapies that should be avoided in certain patients.
Such crossovers are happening more than ever, according to Daryl Pritchard, PhD, vice president of science policy for the Personalized Medicine Coalition, a Washington, D.C.-based education and advocacy group. He says the Food and Drug Administration is relabeling an unprecedented number of drugs for use in diseases for which they were not originally approved.
“Oncology researchers in particular are conducting so-called basket studies,” says Pritchard. “Traditionally, a clinical trial focuses on a particular type of cancer, but a basket study targets a gene mutation, regardless of the tissue or organ involved.”
“This kind of mechanistic approach shortens the process for drug discovery, reducing the time to market, and thereby very significantly reducing drug costs,” McGovern adds.
For him, the approach is more than a novel way of looking beyond the classic organ-systems classification — it’s also a powerful engine for broader discovery. “If I find a genetic signature for a group of patients, and I find a therapy that works for them, then I look for similar signatures in other diseases — and help more patients.”