Tomorrow, the National Institutes of Health (NIH) will mark the seventh annual Rare Disease Day. As part of that gathering, I’d like to share this amateur video. What you’ll hear is an adaptation of a song I once heard sung at a folk festival, but I’ve changed the words. I’m now dedicating this to all of the good people whose lives have been touched by rare diseases.
While the spur-of-the-moment camerawork leaves something to be desired, I love the spirit of this video. It was shot at a gathering of the Moebius Syndrome Foundation in Philadelphia in July 2012. Moebius syndrome is a rare neurological condition, present from birth, that primarily affects the muscles controlling facial expression and eye movement. However, if you watch the video all the way to the end, or read the lyrics at the bottom of this post, I think you’ll find that this song strikes a chord for all such rare conditions.
In the United States, rare diseases are defined as conditions that affect fewer than 200,000 people. That doesn’t sound like a lot. However, when you consider that more than 6,500 conditions fall into this category, rare diseases are a challenge collectively faced by as many as 25 million Americans.
Caption: A variation in the gene that codes for a key blood vessel enzyme makes children prone to fevers, rash, and strokes. Credit: Jonathan Bailey, National Human Genome Research Institute, NIH
A medical mystery that began when a 3-year-old girl came to the NIH Clinical Center here in Bethesda, MD, a decade ago has just been solved. The findings not only promise to help children suffering from a devastating rare disease, but to advance our overall understanding of stroke and other blood vessel disorders.
When researchers first met the little girl, they were baffled. She had a most unusual—and unexplained—constellation of symptoms: recurring fevers, rashes, and strokes, which, sadly, had left her severely disabled. Researchers thought the cause probably wasn’t genetic, because none of the girl’s family members were affected, plus they hadn’t seen other children with similar problems. While they searched for clues, they treated the girl with immunosuppressive drugs to reduce blood vessel inflammation and thereby lower the chance of future strokes.
Caption: Lack of efficacy currently accounts for more than half of all drug failures in Phase II clinical studies (left). If AMP’s target validation efforts improve efficacy by 90% (right), the success rate will rise significantly.
It would seem like there’s never been a better time for drug development. Recent advances in genomics, proteomics, imaging, and other technologies have led to the discovery of more than a thousand risk factors for common diseases—biological changes that ought to hold promise as targets for drugs.
But this deluge of new opportunities has to be put in context: drug development is a terribly difficult business. To the dismay of researchers, drug companies, and patients alike, the vast majority of drugs entering the development pipeline fall by the wayside. The most distressing failures occur when a drug is found to be ineffective in the later stages of development—in Phase II or Phase III clinical studies—after years of work and millions of dollars have already been spent . Why is this happening? One major reason is that we’re not selecting the right biological changes to target from the start.
iStock Caption: Dialysis is often used to treat kidney failure related to diabetes.
My own research laboratory has worked on the genetics of diabetes for two decades. One of my colleagues from those early days, Andrzej Krolewski, a physician-scientist at the Joslin Diabetes Center in Boston, wondered why about one-third of people with type 2 diabetes eventually develop kidney damage that progresses to end-stage renal disease (ESRD), but others don’t. A stealthy condition that can take years for symptoms to appear, ESRD occurs when the kidneys fail, allowing toxic wastes to build up. The only treatments available are dialysis or kidney transplants.
Caption: New patch (left) and traditional Holter (right) for monitoring heart rhythms Credit: iRhythm Technologies (left); Misscurry,Wikimedia Commons (right)
There are thousands of “wellness” apps for smart phones and other mobile devices that will help you count calories, calculate your BMI, monitor your meds, boost your fitness routine, or quit smoking. These are now commonly referred to as “mHealth,” where the “m” stands for mobile technology. While these gadgets may encourage a healthier lifestyle, few of them have been tested rigorously for improved health outcomes over time, and they won’t necessarily keep you out of the ER.
Some of the most dramatic leaps in mHealth will arise when we have small, inexpensive wireless devices with sensors that can monitor your physiology—heart rate, blood pressure, blood sodium and glucose levels, breathing patterns, brain waves, and so on—and then transmit those data to your physician, who can then take actions that may spare you a trip to the hospital or even save your life.