(PHILADELPHIA) — Researchers are advancing
against a rare, deadly lung disease (related to hormones) that no
one had even heard of a decade ago. The disease targets only women,
striking them down during their childbearing years. It can be triggered
by pregnancy, progresses rapidly, and often results in death within
Krymskaya, PhD, Research Associate Professor of Medicine
in the Pulmonary,
Allergy and Critical Care Division at the University
of Pennsylvania School of Medicine, has dedicated the
last several years of her career to combating Lymphangioleimyomatosis
(LAM). The disease causes extensive, abnormal smooth muscle-like
cell proliferation, which invades and destroys the tissues of the
lung by forming cysts, eventually obstructing the flow of air and
leading to lung collapse and failure.
Solving the puzzle…
Globally, researchers tackled the first step, finding out what caused
the cell proliferation and identifying the mutating gene that was
responsible. Next, Krymskaya’s lab at the University of Pennsylvania
was responsible for the breakthrough step of discovering the function
of the gene that caused the cell malfunction, paving the way for
a potential treatment utilizing a medication to inhibit abnormal
growth. This treatment is now in a clinical trial.
As many as 250,000 women may be suffering from LAM, but many are
misdiagnosed with asthma or emphysema or remain undiagnosed. Krymskaya,
who works with the Airways
Biology Initiative at Penn, explains, “the key to combating
this disease is to educate physicians to know how to diagnose LAM
and treat it in its earliest stages before the damage to the lung
is done and a transplant is needed. A biopsy and a high resolution
CT scan, not just an X-ray, are needed to detect LAM.”
Sue Byrnes — who founded The
LAM Foundation, an international non-profit organization focused
on research, after her daughter was diagnosed with LAM — adds,
“This heart wrenching disease strikes women as they are beginning
their careers, getting married and starting families, just when
their futures look so bright. Women with LAM often struggle to breathe.
They experience lung collapses, chest pain, cough, and can become
extremely fatigued. Many of them develop a benign kidney tumor.
Supplemental oxygen is inevitable, and a lung transplant, which
usually buys them only a few years, is the very last resort for
One woman’s struggle…
43-year-old Sheila Egan Addis, a Philadelphia theatrical performer
and mother of two, who lives in Center City, started suffering from
alternating collapsed lungs when she turned 30. “It felt like
a sharp pain in my upper back, like I’d pulled a muscle when
I tried to take a deep breath,” Egan Addis comments. After
the third time each lung had collapsed, surgeons went in to restore
some of the lung function. Nine years after she began suffering
symptoms, a Penn pulmonologist finally diagnosed her with LAM disease.
“Finally, it all made sense,” Egan Addis adds.
Two years ago, her right lung collapsed again and she was operated
on. Egan Addis has since lost some more lung function. She says
it does take a toll on a performer in live musical theater, “I
don't have the stamina that I used to. I can't do a lot of running
around and singing. I have to think about it before taking on a
challenging role. The pace of live theater can be very tiring and
There is hope…
Krymskaya’s discovery in 2002 revealed that abnormal smooth
muscle-like LAM cells invading the lungs are due to the loss of
growth control by tuberous sclerosis (a genetic disorder which causes
tumors to form in organs) complex proteins — and furthermore,
Krymskaya then discovered that growth can potentially be controlled
by a drug (FDA-approved Rapamycin), which mimics the function of
the missing proteins. Krymskaya made the link between similar basic
research found in flies and applied it to humans, opening the door
for the first-ever LAM treatment clinical trial now underway.
Globally, researchers are excited about discovering more about
LAM because of the close relationship between it and other diseases.
“If we solve this puzzle, it may very well lead to answers
regarding other deadly diseases like heart and vascular disease,
cancer and diabetes,” Krymskaya notes.
Funding for LAM research was provided through the LAM Foundation
as well as various grants from the National Institutes of Health.
PENN Medicine is a $2.9 billion enterprise
dedicated to the related missions of medical education, biomedical
research, and high-quality patient care. PENN Medicine consists
of the University of Pennsylvania School of Medicine (founded in
1765 as the nation's first medical school) and the University of
Pennsylvania Health System.
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& World Report's most recent ranking of top research-oriented
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the School of Medicine is recognized worldwide for its superior
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and leaders of academic medicine.
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all of which have received numerous national patient-care honors [Hospital
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