The discovery marks the first effective therapy scientists have ever found for the lung disease known as lymphangioleiomyomatosis, or LAM, a rare condition in women often discovered during pregnancy, said Dr. Mark Brantly, a University of Florida professor of medicine and one of the co-authors of the paper.
“Like many lung diseases, this was a disease of unknown cause. We really had no therapy. We used to manipulate hormones, and it really just made the women sick. It was really sad. I used to watch these women, on a regular basis, die over time, with nothing to really offer them,” said Brantly, who also serves as chief of the division of pulmonary, critical care and sleep medicine in the UF College of Medicine. “Now we have a therapy that not only stops the progress of the disease but improves lung function over time.”
Known as the MILES Trial, the clinical trial was led by the University of Cincinnati and took place at sites across the United States as well as in Canada and Japan. UF was the trial site for Florida. The National Institutes of Health and other agencies funded the study.
According to the study’s findings, patients who received the drug rapamycin, also known as sirolimus, for one year performed significantly better on lung function tests than those who received the placebo. During the second year of the trial, the researchers stopped administering the therapy and observed patients.
The patients’ conditions worsened when they stopped receiving the drug, likely meaning those who receive this therapy will need to continue taking it over time.
“It is a potent drug, but we do not use it in concentrations high enough to cause significant problems,” Brantly said. “It seems to be very effective.”
LAM is similar to a slow-growing cancer, Brantly says. But that is something scientists have only begun to understand in the past decade, when they began unraveling the molecular complexities of the disease — complexities that are still not fully understood.
In patients with the disease, mutations spur tumor-suppressing signals in the body to switch off, causing a burst of cell growth as smooth muscle cells invade the lungs. These cells can choke off airways and cause cysts to form. Because of this cell growth, patients with LAM also are prone to developing abdominal tumors, Brantly said.
Studies on LAM cells pinpointed a cell-signaling pathway, which if blocked, could throw the switch back, putting an end to the cell population explosion. Because rapamycin blocks that pathway, the scientists began to test it, first in a small number of women and then in the clinical trial.
Because so few women have this disease — there are only 2,000 patients known worldwide, according to the LAM Foundation — researchers banded together to complete the trial.
“Our founder started this foundation 16 years ago when her daughter was diagnosed with LAM,” said Jill Raleigh, executive director of the LAM Foundation, which helped fund the trial and recruit patients. “She found one article about LAM. To be able to say there is a treatment now is unbelievable.”
Though not all LAM patients respond to the treatment, the discovery marks a giant milestone in helping patients with the disease, Brantly said.
“We want to help patients understand, this is one treatment,” Raleigh said. “We are still not there yet. We still have a long way to go, but there is hope now. Before (March 16) all we could say is ‘There’s no treatment.’ Now at least there is that feeling of hope, a treatment and more on the horizon.”
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