On the LAM

CITYPAPER.NET EXCLUSIVE: Local researchers have been key to understanding a little-known, fatal disease.

by Zach Pontz

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Published: Mar 28, 2007

Medicine

LAM, a crippling lung disease that first appeared in medical documents in 1919, is so rare that the foundation dedicated to its research knows of just one woman in Philadelphia who's been diagnosed. But despite the rarity of cases, much work is being done by two local researchers to shed light on the disease.

Sheila Egan-Addis, a 43-year-old stage actress, lives in Center City with her husband and two children. She first noticed symptoms that would later be diagnosed as LAM — short for pulmonary lymphangioleiomyomatosis — when she was 30, but wasn't diagnosed until four years ago. "I can't run, I really have to watch it, make sure I get enough sleep. I try not to allow it to affect my everyday life, but I've found that I don't have the endurance to do consecutive shows. My body can't take it. I need to rest after a run. I wear down very easily."

Luckily, as the disease becomes more debilitating, so does the knowledge and understanding of it among doctors and scientists. In 1999, Vera Krymskaya was a research associate studying cell function and growth at the University of Pennsylvania when a mentor told her about a conference called LAMposium that he'd just attended.

What she learned was that LAM is caused by smooth muscle cells (spindle-shaped cells located in hollow organs such as the abdominal cavity and in male and female reproductive tracts) that attack the lung. And that's where the knowledge ended.

"Every doctor — or doctor just starting out — hopes for an opportunity of coming across a situation such as this, a disease so unknown," says Krymskaya. "I was immediately taken with learning more."

So the next year, Krymskaya contacted Sue Byrnes, founder and then executive director of the LAM Foundation (www.thelamfoundation.org), to obtain a $25,000 grant to study the disease. The following year, Dr. Elizabeth Henske of Fox Chase Cancer Center discovered the gene that caused the disease.

Using that gene, Krymskaya said she determined that the abnormal growth and movement of the LAM cells were due to the loss of function of a protein called tuberous sclerosis complex 2 (TSC2). This allowed Krymskaya and other scientists to determine that the FDA-approved drug rapamycin could combat LAM because of its ability to mimic the function of the missing proteins.

That led to the first clinical trial to be performed on LAM patients.

The MILES Trial, which recently started in Cincinnati, will administer rapamycin to some patients and a placebo to others in an effort that study leader Dr. Frank McCormack says is going well. "We have enrolled four patients, and three more are scheduled this month. We have a long list of interested patients and we are optimistic that the trial will meet its enrollment targets," says McCormack, who is quick to add: "Vera [Krymskaya] has been invaluable to the LAM effort. Her laboratory was the first to demonstrate the relevance of tuberous sclerosis discoveries in worms, flies and rodents to patients with LAM. Her studies have provided several critical elements in building a rationale for clinical trials of rapamycin in LAM patients."

Although she's supportive of the trial, actress Egan-Addis hasn't yet decided whether she'll participate. "It's up in the air. I need to learn more about the side effects," she says, referring to nausea and rashes, among other drawbacks. "But I know I qualify, and we'll see."

Much has been learned about LAM since Krymskaya's initial introduction to the disease. Found almost exclusively in women of child-bearing age, LAM is so hard to diagnose that a high-resolution CT scan and biopsy is usually necessary. In fact, it's often misdiagnosed as asthma, emphysema or pulmonary bronchitis.

To date, only about 1,200 women worldwide have registered with the LAM Foundation, but doctors believe that as many as 250,000 to 300,000 women may have LAM. According to the foundation's Web site, it's caused by an irregular muscle cell that invades the lung tissue; it then attaches itself to the walls of the airways, which ultimately prevents the lungs from distributing oxygen to the rest of the body, in effect, suffocating the individual.

Krymskaya says that the disease isn't as inconsequential as the small diagnosis rate might indicate, and that ongoing research is vital. "It is linked with other more devastating diseases — cancer, many lung diseases," she notes.

Says Henske of Fox Chase Cancer Center, "We believe that understanding LAM will help us understand other diseases in which estrogen plays a role, including breast cancer. The biochemical origins of LAM are linked with diabetes, restenosis after coronary artery stenting, and many types of cancer."

Though relatively little is known, the rate of discovery is encouraging.

"It's been a remarkably quick pace from discovery [of the cause of LAM] to the clinical trial," says Krymskaya. "Hopefully, by studying LAM and finding the relation in more popular diseases, we will be able to draw more attention to this one."

(editorial@citypaper.net)

 

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