Whether by snail mail, email, or social media, it’s the time of year for catching up with family and friends. As NIH Director, I’m also fortunate to hear from some of the amazing people who’ve been helped by NIH research. Among the greetings to arrive in my inbox this holiday season is this incredible video from a 15-year-old named Aaron, who is fortunate enough to count two states—Alabama and Colorado—as his home.
As a young boy, Aaron was naturally athletic, speeding around the baseball diamond and competing on the ski slopes in freestyle mogul. But around the age of 10, Aaron noticed something strange. He couldn’t move as fast as usual. Aaron pushed himself to get back up to speed, but his muscles grew progressively weaker.
Tags: anti-HMGCR myopathy, antibodies, autoimmunity, childhood diseases, clinical research, clinical trials, immunology, intravenous immunoglobulins, IVIG, muscle, muscle diseases, muscular dystrophy, myopathy, statins
More than 17 million people around the world are living with cerebral palsy, a movement disorder that occurs when motor areas of a child’s brain do not develop correctly or are damaged early in life. Many of those affected were born extremely prematurely and suffered brain hemorrhages shortly after birth. One of the condition’s most common symptoms is crouch gait, which is an excessive bending of the knees that can make it difficult or even impossible to walk. Now, a new robotic device developed by an NIH research team has the potential to help kids with cerebral palsy walk better.
What’s really cool about the robotic brace, or exoskeleton, which you see demonstrated above, is that it’s equipped with computerized sensors and motors that can detect exactly where a child is in the walking cycle—delivering bursts of support to the knees at just the right time. In fact, in a small study of seven young people with crouch gait, the device enabled six to stand and walk taller in their very first practice session!
Tags: bioengineering, biomechanics, birth injury, brain injury, cerebral palsy, childhood disorder, CP, crouch gait, gait, knees, mobility, motor skills, movement disorders, muscular dystrophy, neurological disorders, orthotic ankle braces, physical disability, premature birth, rehabilitation medicine, robotic exoskeleton, technology
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
Matthew Disney grew up in a large family in Baltimore in the 1980s. While his mother worked nights, Disney and his younger brother often tagged along with their father in these pre-Internet days on calls to fix the microfilm machines used to view important records at hospitals, banks, and other places of business. Watching his father take apart the machines made Disney want to work with his hands one day. Seeing his father work tirelessly for the sake of his family also made him want to help others.
Disney found a profession that satisfied both requirements when he fell in love with chemistry as an undergraduate at the University of Maryland, College Park. Now a chemistry professor at The Scripps Research Institute, Jupiter, FL, Disney is applying his hands and brains to develop a treatment strategy that aims to control the progression of a long list of devastating disorders that includes Huntington’s disease, amyotrophic lateral sclerosis (ALS), and various forms of muscular dystrophy.
The 30 or so health conditions on Disney’s list have something in common. They are caused by genetic glitches in which repetitive DNA letters (CAGCAGCAG, for example) in transcribed regions of the genome cause some of the body’s cells and tissues to produce unwieldy messenger RNA molecules that interfere with normal cellular activities, either by binding other intracellular components or serving as templates for the production of toxic proteins.
The diseases on Disney’s list also have often been considered “undruggable,” in part because the compounds capable of disabling the lengthy, disease-causing RNA molecules are generally too large to cross cell membranes. Disney has found an ingenious way around that problem . Instead of delivering the finished drug, he delivers smaller building blocks. He then uses the cell and its own machinery, including the very aberrant RNA molecules he aims to target, as his drug factory to produce those larger compounds.
Disney has received an NIH Director’s 2015 Pioneer Award to develop this innovative drug-delivery strategy further. He will apply his investigational approach initially to treat a common form of muscular dystrophy, first using human cells in culture and then in animal models. Once he gets that working well, he’ll move on to other conditions including ALS.
What’s appealing about Disney’s approach is that it makes it possible to treat disease-affected cells without affecting healthy cells. That’s because his drugs can only be assembled into their active forms in cells after they are templated by those aberrant RNA molecules.
Interestingly, Disney never intended to study human diseases. His lab was set up to study the structure and function of RNA molecules and their interactions with other small molecules. In the process, he stumbled across a small molecule that targets an RNA implicated in a rare form of muscular dystrophy. His niece also has a rare incurable disease, and Disney saw a chance to make a difference for others like her. It’s a healthy reminder that the pursuit of basic scientific questions often can lead to new and unexpectedly important medical discoveries that have the potential to touch the lives of many.
 A toxic RNA catalyzes the in cellulo synthesis of its own inhibitor. Rzuczek SG, Park H, Disney MD. Angew Chem Int Ed Engl. 2014 Oct 6;53(41):10956-10959.
Disney Lab (The Scripps Research Institute, Jupiter, FL)
Disney NIH Project Information (NIH RePORTER)
NIH Support: Common Fund; National Institute of Neurological Disorders and Stroke
Tags: ALS, amyotrophic lateral sclerosis, brain disorder, chemistry, drug delivery, drugs, Huntington's disease, inherited disease, muscular dystrophy, neurodegenerative disorders, NIH Director’s 2015 Pioneer Award, rare disease, RNA
Bill Bement describes himself as a guy who “passionately, obsessively, and almost feverishly” loves to study cells. His excitement comes through in our final installment of the American Society for Cell Biology’s Celldance 2014. Bement, an NIH grantee at the University of Wisconsin, Madison, shares his scanning confocal microscope with us for this fascinating glimpse into the rapid response of cells to repair holes, tears, and other structural damage in their protective outer membranes.
For most people, this damage response runs on biochemical autopilot, sealing any membrane break within seconds to keep the cell viable and healthy. But some people inherit gene mutations that make sealing and patching difficult, particularly in cells that operate under repetitive mechanical stress. For example, some forms of muscular dystrophy stem specifically from an inherited inability to repair breaks in the cell membrane of skeletal muscle cells. In one type of disease that affects both skeletal and cardiac muscle, a gene mutation alters the shape of a protein called dysferlin, which normally binds annexin proteins that, as noted in the video, play a vital role in patching holes. In the presence of a glitch in dysferlin, the rapid chain of biochemical events needed to enable such repair breaks down.
There’s still an enormous amount to learn about cell membrane repair, so it will be interesting to see what Bement’s microscope and camera will show us next.
Bement Lab, University of Wisconsin-Madison
Celldance 2014, American Society for Cell Biology
NIH Support: National Institute of General Medical Sciences