Research on an uncommon illness piggybacks on the discoveries in other fields to test a potential therapy.
Graphic: Patrick J. Lynch
There are hundreds of rare diseases — affecting just a few thousand people around the world, and some right here in the Delaware Valley. It can be hard to find treatments for illnesses that have to compete for attention with more common diseases like cancer or Alzheimer’s. But for one unusual disease called LAM, researchers are testing what might turn out to be the first treatment developed.
Graphic: Patrick J. Lynch
Listen to First treatment for rare lung disease: [audio:sci20081203lung.mp3]
Listen to Dr. Elizabeth Henske, director of the LAM Center of Excellence at Brigham and Women’s Hospital, speak about her discovery of the genes that cause LAM and the mysteries she’s currently trying to solve.
Listen to Dr. Elizabeth Henske: [audio:sci20081203xtra.mp3]
Rare disease bank gets boost
A Philadelphia tissue bank has received a federal grant to expand its offerings to researchers.
Listen to Rare disease bank gets boost: [audio:sci20081204ndri.mp3]
Transcript – First treatment for rare lung disease:
In her spotless Elkins Park home, Alanna Nelson thinks back to before the diagnosis. She was in her early thirties, a work-aholic, and healthy. Until one unusual incident.
Nelson: About 8 years ago I had a random lung collapse. And went to the doctors, they saw it was a lung collapse and they just said, oh it’s unusual but it sometimes happens to people and they just said go about your life, you’ll be fine.
And she was fine, for about seven more years, until another unexpected lung collapse sent her to the hospital for three weeks. Her proper diagnosis took some time, likely because no one treating her was familiar with the disease: Lymphangioleiomyomatosis (LAM). Nelson was devastated.
Nelson: Oh my gosh, how do I have this disease I can’t spell. Still probably can’t spell it completely. A disease you can’t spell, a disease you’ve never heard of.
And a disease you can’t cure. It’s caused by genetic mutation — sometimes inherited, sometimes random — that results in lung cysts, which eventually consume the lungs, making breathing difficult. Some women — it mostly strikes women — go on oxygen, others seek a lung transplant. But even such a dramatic fix doesn’t always work, says Nelson’s doctor Robert Kotloff at the University of Pennsylvania.
Kotloff: The one curious thing with lung transplant for women with LAM is that it’s now been shown on multiple occasions that the disease can occur after transplantation. That’s not a reason to avoid the procedure, but it is something women need to be aware of as they pursue that as an option.
LAM affects about 1500 women worldwide, which is virtually nil in the world of disease statistics. Consider that each week about 1500 people die from Alzheimer’s, each day 1500 people die from cancer. Often, rare conditions have to piggy back on the discoveries in other fields because there are so few people studying them, and LAM is no exception. About the time Alanna Nelson experienced her first lung collapse, a Philadelphia-based researcher discovered that the gene that causes LAM also causes a disease called tuburous sclerosis –about which researchers knew much more. Peter Crino, in UPenn’s neurology department, says the tuburous sclerosis mutations are known to pop the lid off a protein called mTOR.
Crino: So mTOR is essentially signaling unchecked.
Leaving cells to behave in ways they shouldn’t. But there is a drug – rapamycin – that can tame mTOR.
Crino: Rapamycin serves to specifically antagonize mTOR and almost acts as though you had replaced the genes basically back to do their normal function.
Crino and others are part of clinical trials to test how rapamycin works in patients with tuberous sclerosis and LAM. Doctor Kotloff points out that even rapamycin was borrowed from another field.
Kotloff: In fact the drug that we’re looking at to treat LAM is a drug that was developed for transplantation. So it’s a good example of attention being paid to one area that’s very common but then being able to use the knowledge learned in a common area and apply that to an uncommon disease.
Rapamycin has side effects and the trials are still in progress. Researchers expect to know whether it works safely in a few years.
Transcript – Rare disease bank gets boost:
The National Disease Research Interchange provides human tissue to researchers in fields like stem cells, diabetes, and rare diseases. For one of these rare diseases, called lymphangioleiomyomatosis or LAM, the interchange is the primary tissue supplier in the world. Elizabeth Henske, a LAM researcher at Brigham and Women’s Hospital discovered the genes for LAM while working in Philadelphia, says getting tissue alive is no small feat.
Henske: Many women with LAM have lung transplants, so there’s a great deal of tissue available. But the challenge is how to get it to the researchers and get it to us very quickly, so that we can study the cells while they’re still alive in the tissue.
Henske says the interchange will get tissue to researchers within four hours of transplant – which is remarkable, given that the procedures are unplanned. The organization received more than seven million dollars from the National Institutes of Health to expand its LAM and other tissue supplies.