Precision Medicine: Making Warfarin Safer

Blood sample for PT INR test, diagnosis for coagulation disease

Caption: Finding the right dose of the drug warfarin can be tricky, even with this standard test to measure how fast a person’s blood clots.
Credit: Thinkstock/jarun011

Every year, thousands of older Americans require emergency treatment to stop bleeding caused by taking warfarin, a frequently prescribed blood-thinning pill. My own mother received this drug in her later years, and her doctors encountered significant challenges getting the dose right. The problem is too much warfarin causes potentially serious bleeding, while too little leaves those who need the drug vulnerable to developing life-threatening clots in their legs or heart. The difference between too little and too much is distressingly small. But what if before writing a prescription, doctors could test for known genetic markers to help them gauge the amount of warfarin that a person should take?

Such tests have been available to doctors and patients for a few years, but they have not been widely used. The recent results of a national clinical trial offer some of the most convincing evidence that it’s time for that to change. In this study of 1,650 older adults undergoing elective hip or knee surgery, patients whose genetic makeup was used to help determine their dose of warfarin were less likely to suffer adverse events, including major bleeding. This trial marks an encouraging success story for the emerging field of pharmacogenomics, the study of how the variations in our genes affect our responses to medicines.

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Another Milestone in the Cystic Fibrosis Journey

Avalyn Mahoney

Caption: Two-year-old Avalyn is among the cystic fibrosis patients who may be helped by targeted drugs.
Credit: Brittany Mahoney

As NIH Director, I often hear stories of how people with serious diseases—from arthritis to Zika infection—are benefitting from the transformational power of NIH’s investments in basic science. Today, I’d like to share one such advance that I find particularly exciting: news that a combination of three molecularly targeted drugs may finally make it possible to treat the vast majority of patients with cystic fibrosis (CF), our nation’s most common genetic disease.

First, a bit of history! The first genetic mutation that causes CF was discovered by a collaborative effort between my own research lab at the University of Michigan, Ann Arbor, and colleagues at the Hospital for Sick Children in Toronto—more than 25 years ago [1]. Years of hard work, supported by the National Institutes of Health and the Cystic Fibrosis Foundation, painstakingly worked out the normal function of the protein that is altered in CF, called the cystic fibrosis transmembrane regulator (CFTR). Very recently new technologies, such as cryo-EM, have given researchers the ability to map the exact structure of the protein involved in CF.

Among the tens of thousands of CF patients who stand to benefit from the next generation of targeted drugs is little Avalyn Mahoney of Cardiff by the Sea, CA. Just a few decades ago, a kid like Avalyn—who just turned 2 last month—probably wouldn’t have made it beyond her teens. But today the outlook is far brighter for her and so many others, thanks to recent advances that build upon NIH-supported basic research.

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Precision Oncology: Gene Changes Predict Immunotherapy Response

Cancer Immunotherapy

Caption: Adapted from scanning electron micrograph of cytotoxic T cells (red) attacking a cancer cell (white).
Credits: Rita Elena Serda, Baylor College of Medicine; Jill George, NIH

There’s been tremendous excitement in the cancer community recently about the life-saving potential of immunotherapy. In this treatment strategy, a patient’s own immune system is enlisted to control and, in some cases, even cure the cancer. But despite many dramatic stories of response, immunotherapy doesn’t work for everyone. A major challenge has been figuring out how to identify with greater precision which patients are most likely to benefit from this new approach, and how to use that information to develop strategies to expand immunotherapy’s potential.

A couple of years ago, I wrote about early progress on this front, highlighting a small study in which NIH-funded researchers were able to predict which people with colorectal and other types of cancer would benefit from an immunotherapy drug called pembrolizumab (Keytruda®). The key seemed to be that tumors with defects affecting the “mismatch repair” pathway were more likely to benefit. Mismatch repair is involved in fixing small glitches that occur when DNA is copied during cell division. If a tumor is deficient in mismatch repair, it contains many more DNA mutations than other tumors—and, as it turns out, immunotherapy appears to be most effective against tumors with many mutations.

Now, I’m pleased to report more promising news from that clinical trial of pembrolizumab, which was expanded to include 86 adults with 12 different types of mismatch repair-deficient cancers that had been previously treated with at least one type of standard therapy [1]. After a year of biweekly infusions, more than half of the patients had their tumors shrink by at least 30 percent—and, even better, 18 had their tumors completely disappear!

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Built for the Future. Study Shows Wearable Devices Can Help Detect Illness Early

Michael Snyder wearing monitors

Caption: Stanford University’s Michael Snyder displays some of his wearable devices.
Credit: Steve Fisch/Stanford School of Medicine

Millions of Americans now head out the door each day wearing devices that count their steps, check their heart rates, and help them stay fit in general. But with further research, these “wearables” could also play an important role in the early detection of serious medical conditions. In partnership with health-care professionals, people may well use the next generation of wearables to monitor vital signs, blood oxygen levels, and a wide variety of other measures of personal health, allowing them to see in real time when something isn’t normal and, if unusual enough, to have it checked out right away.

In the latest issue of the journal PLoS Biology [1], an NIH-supported study offers an exciting glimpse of this future. Wearing a commercially available smartwatch over many months, more than 40 adults produced a continuous daily stream of accurate personal health data that researchers could access and monitor. When combined with standard laboratory blood tests, these data—totaling more than 250,000 bodily measurements a day per person—can detect early infections through changes in heart rate.

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Happy New Year: Looking Back at 2016 Research Highlights

Science Breakthroughs of the Year 2016Happy New Year! While everyone was busy getting ready for the holidays, the journal Science announced its annual compendium of scientific Breakthroughs of the Year. If you missed it, the winner for 2016 was the detection of gravitational waves—tiny ripples in the fabric of spacetime created by the collision of two black holes 1.3 billion years ago! It’s an incredible discovery, and one that Albert Einstein predicted a century ago.

Among the nine other advances that made the first cut for Breakthrough of the Year, several involved the biomedical sciences. As I’ve done in previous years (here and here), I’ll kick off this New Year by taking a quick look of some of the breakthroughs that directly involved NIH support:

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