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 . 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.
Tags: CF, CFTR, clinical research, cystic fibrosis, Cystic Fibrosis Foundation, drug development, F508del, genetics, genomics, ivacaftor, Kalydeco, next-generation drugs, Orkambi, precision medicine, rare diseases, tezacaftor, Vertex Pharmaceuticals
My father was a folk song collector, and I grew up listening to the music of Woody Guthrie. On July 14th, folk music enthusiasts will be celebrating the 105th anniversary of Guthrie’s birth in his hometown of Okemah, OK. Besides being renowned for writing “This Land is Your Land” and other folk classics, Guthrie has another more tragic claim to fame: he provided the world with a glimpse at the devastation caused by a rare, inherited neurological disorder called Huntington’s disease.
When Guthrie died from complications of Huntington’s a half-century ago, the disease was untreatable. Sadly, it still is. But years of basic science advances, combined with the promise of innovative gene editing systems such as CRISPR/Cas9, are providing renewed hope that we will someday be able to treat or even cure Huntington’s disease, along with many other inherited disorders.
Tags: adult neurons, brain, CAG, CRISPR/Cas9, gene editing, genetics, genomics, HTT gene, huntingtin, Huntington's disease, inherited disease, misfolded proteins, muscular dystrophy, mutation, neurodegenerative disorders, neurological disorders, neuron, rare disease, sickle cell disease, striatum
Microbes that live in dirt often engage in their own deadly turf wars, producing a toxic mix of chemical compounds (also called “small molecules”) that can be a source of new antibiotics. When he started out in science more than a decade ago, Michael Fischbach studied these soil-dwelling microbes to look for genes involved in making these compounds.
Eventually, Fischbach, who is now at the University of California, San Francisco, came to a career-altering realization: maybe he didn’t need to dig in dirt! He hypothesized an even better way to improve human health might be found in the genes of the trillions of microorganisms that dwell in and on our bodies, known collectively as the human microbiome.
Tags: 2016 NIH Director’s Pioneer Award, analytical chemistry, antibiotics, bacteria, biochemistry, biofilm, digestion, gastrointestinal disease, gastrointestinal tract, genetic engineering, genetics, GI tract, gut, gut bacteria, gut microbiome, heart disease, microbes, microbiome, microbiota, microorganisms, obesity, probiotics, small molecules, synthetic gut community
Every person’s genetic blueprint, or genome, is unique because of variations that occasionally occur in our DNA sequences. Most of those are passed on to us from our parents. But not all variations are inherited—each of us carries 60 to 100 “new mutations” that happened for the first time in us. Some of those variations can knock out the function of a gene in ways that lead to disease or other serious health problems, particularly in people unlucky enough to have two malfunctioning copies of the same gene. Recently, scientists have begun to identify rare individuals who have loss-of-function variations that actually seem to improve their health—extraordinary discoveries that may help us understand how genes work as well as yield promising new drug targets that may benefit everyone.
In a study published in the journal Nature, a team partially funded by NIH sequenced all 18,000 protein-coding genes in more than 10,500 adults living in Pakistan . After finding that more than 17 percent of the participants had at least one gene completely “knocked out,” researchers could set about analyzing what consequences—good, bad, or neutral—those loss-of-function variations had on their health and well-being.
Tags: All of Us, All of Us Research Program, APOC3, cardiology, cholesterol, DNA, drug development, drug targets, gene knockouts, gene mutations, genetics, genomics, heart attack, heart disease, human knockout, myocardial infarction, Pakistan, Pakistan Rise of Myocardial Infarction Study, PLA2G7, triglycerides