A young woman is out of breath after walking up a half-flight of stairs. Her symptoms appear to be that of emphysema. Yet she has never smoked (the leading cause of emphysema) nor has any associated risk factors, and her chest x-rays appear normal. Would one ever suspect a lung disease known as LAM?
LAM, or lymphangioleiomyomatosis, is a rare lung disease that mostly affects women of childbearing age. The disease begins when abnormal, muscle-like cells from other parts of the body invade the lungs. Once in the lungs, these LAM cells metastasize, or grow out of control, eventually destroying normal lung tissue.
The disease begins slowly, often with a slow progression of trouble breathing, sometimes leading to a collapsed lung or end-stage lung disease. The prognosis is often devastating—ongoing assistance of an oxygen tank to breathe, a lung transplant or death at an early age.
A Wolf in Sheep’s Clothing
LAM usually affects women ages 20 to 40. “Of all human diseases there are almost no diseases that have this extremely strong gender predisposition, “ said Elizabeth Henske, MD, director of the BWH Center for LAM Research and Clinical Care. “LAM has an even stronger female predisposition than breast cancer.”
Many women who have LAM may not know they have it, since the signs and symptoms are similar to those of other diseases, such as asthma, emphysema, and bronchitis.
“Young women who were previously healthy and who have young families are facing this life-threatening disease that can progress unexpectedly with the prospect of losing their ability to live a normal life,” said Henske. “Sometimes these women or their physicians think that it is normal to be a little short of breath and tired due to having young children or just being very busy in life and career. So symptoms can also mimic normal, busy life.”
Helping Patients Breath Better
LAM is caused by a gene mutation that is also responsible for another disease known as tuberous sclerosis complex (TSC). TSC leads to non-malignant tumors forming in many different organs, such as the brain, eyes, heart, kidney and skin.
LAM and TSC are intimately related, according to Henske. Among women affected by TSC, 30 to 50 percent will also develop LAM.
Henske and her team devote their time to studying LAM cells in order to one day improve treatments against the debilitating disease. The research team focuses on three main objectives.
The first is to understand the mechanisms that cause LAM cells by answering the following questions: Why does LAM only affect women? Why do benign LAM cells metastasize? Why are normal lung cells destroyed when LAM cells invade the lungs?
Secondly, the team spends time trying to identify better LAM biomarkers, and ways to track the progression of LAM.
“Our team is working to identify metabolites, compounds or cytokines in the blood that would allow us to track the disease better,” said Henske.
Developing new blood tests for LAM, Henske believes, will improve how clinicians manage patients.
“The only way to know if a woman with LAM is getting better or worse is to track her lung function, basically how much air a patient can blow out through a tube. This is not a very precise test,” said Henske. “We want to have a more precise way to know if LAM is getting better or worse, such as a blood test. Such a test can also help a clinician tell if the LAM is responding to treatment.”
Lastly, Henske’s research team is also involved in clinical trials testing two drugs in combination, each of which is FDA-approved to treat other diseases, to find out if they may also be safe and effective for the treatment of LAM.
“The current treatment we have available against LAM only stops the cells from growing. As soon as the drug is stopped, the cells grow again,” said Henske. “We are trying to find a treatment that causes the LAM cells to go away all together. We are using a combination of two drugs and treating women for six months, and then following them for six months off treatment. By doing this, we want to find out if after the two-drug combo is stopped, will the disease come roaring back or will the disease remain at a stable level.”
For now, Henske’s research continues to drive not only the overall national efforts in finding better treatments against LAM; but her work is also one of passion to help women struggling with the disease.
“Fourteen years ago I first attended a meeting hosted by the LAM Foundation. At the time I had young children myself and many of these women who had LAM also had young children, and they were literally struggling to breath,” recalled Henske. “I realized that the work we were doing could change the course of their lives. The chance to really influence the lives of these women was pivotal in my decision to focus more of my research on LAM.”