HEALTH

Is every disease a rare disease?

The promise of the Precision Medicine Initiative is a specific treatment for a specific disease. A logical extension of that thinking is that perhaps we should be viewing every disease as a rare disease. That was the focus of a HUBWeek panel hosted by STAT.

STAT’s national biotech reporter, Damian Garde, led the panel. He was joined by Dr. Anna Greka, a researcher at the Broad Institute; Michael Ringel, a senior partner and managing director at the Boston Consulting Group; Dr. Matthew Meyerson, director of the Center for Cancer Genome Discovery at the Dana-Farber Cancer Institute; and Dr. David Grayzel, a partner at Atlas Venture, which invests in novel therapeutics, often those near a first human clinical test. Here are excerpts of their discussion, edited for length and clarity.

What do we mean when we say precision medicine, and how does that contrast with ways we’ve been treating disease for a century?

Ringel: You can think of the arc of medicine as a very long arc. From treating disease as a set of symptoms to a now deeper understanding, where I understand the underlying biology and I can treat the underlying biology. We’re somewhere on that path, and precision medicine is about taking the next step. It’s about advancing the state of knowledge a little bit beyond where we are. It usually connotes genomics and companion diagnostics, but it doesn’t have to.

Is personalized medicine just a biotech buzz phrase?

Greka: I think to some extent it’s a buzzword, but to some extent it’s a reality that is dictated by our own success in genomics. We have made a tremendous investment, as humanity, as the United States, as Boston, to have a road map. The human genome is known to us now, and we better do something to harness that to treat disease.

In my field of kidney disease, there hasn’t really been much innovation for about 25 years. And a big part of it is because we had a very generic understanding of the disease. In my field, I think it’s the only path forward. I don’t necessarily see it as a hyped-up term, but rather the only way to put something in the pipeline for therapeutics.

Read more: The NIH, in pursuit of precision medicine, tries to avoid ghosts of its past

The Precision Medicine Initiative will gather a great deal of data. What will researchers be able to make of it?

Ringel: The Human Genome Project was completed about 15 years ago. Big splash. It was supposed to change lives, but a lot didn’t happen. One genome isn’t that helpful for drawing inferences about what’s associated with disease. Once the cost of genome sequencing came down, you could start to do it on large data patient sets and now you can look for associations. These are called genome-wide association studies. The first one wasn’t done until 2007, and, even then, it was pretty rare and expensive. Now there are hundreds of them and the Precision Medicine Initiative will push this further. You can start to find correlations in something that’s in the genes and in the disease state. That doesn’t tell you everything, but it gives you clues about where to look.

Greka: Drug targets are hard to find. This is like looking for a needle in a haystack. I’d like to bring the focus back to rare disease as an opportunity to start to understand diseases that perhaps affect very small groups of people, but then you can find a target. We can use the power of genomics to sequence a few thousand people with a particular disease.

Meyerson: But just because we understand the mechanism of a disease, doesn’t mean that we can find a drug for it. And that’s one of the real challenges of precision medicine. Relatively speaking, genetics and genomics are easy compared to drug discovery. Take cystic fibrosis: it was more than 25 years from gene discovery to drug discovery.

One of the important caveats in the whole field of precision of medicine is that just because we know the cause of a disease doesn’t mean that we can get to a solution for it. In cancer, it’s the same way. Most of the mutated genes in cancer we have no drug for. Not only do we not have a drug, we have no concept of where to start making one. Going from a molecular mechanism to building a drug is one of the biggest challenges.

Grayzel: To layer onto that: once I can identify a mutation, what’s its role? Is it involved in the initiation of the disease, in the progression, maintenance?

Does breaking down things into small populations de-incentivize investments into great big disease states or pose public health concerns?

Ringel: It is not a priori true that precision means fragmentation. Though it often does. Maybe there’s another way to think about this. There’s something called the International Classification of Disease. It lists all the diseases that are out there. We’re in ICD 10, which is the 10th incarnation of ICD. It started in the late 1800s with ICD 1, which had 174 diseases. Today, ICD 10 has over 8,000. Now some of those are just crazy specific, but some are related to deeper understand of the biology.

Read more: Episode 4: A shoppers guide to the genome sequencing market

The example that sticks out for me is in ICD 1, they have: “blood disease.” In ICD 10, we have 34 different leukemias. We went from “blood disease” to 34 different leukemias, and it’s what we have to do to treat patients: to be thinking about what is the underlying mechanism for each person’s disease so they can get the right treatment. It’s not an option to say, “I wish it were still just blood disease.”

Someday, Alzheimer’s disease and cancer probably won’t be single diseases but rather series of smaller diseases or pathways. How do we get there?

Greka: There’s the radical idea of thinking of every patient as a potential contributor to the scientific inquiry. This comes into all kinds of other issues, like ethics, around who manages the data and how well the data are protected. But the idea of being able to genomically define as many individuals as possible on the planet and then being able to follow them over time and understand something about the phenotypes we could then start to better define disease. The idea that we could all agree that every time we walk into a hospital and we have some test taken, we will be sequenced and have this data linked to our medical data, and somehow this will be safe and managed by people who are responsibility handling this data to harness for the greater good — that’s an idea that has been discussed. Are we all ready for it? You tell me.