A life-like mask sits at the top of Zsolt Urban’s tallest
bookshelf. It bears the likeness of a
12-year-old girl with freckles, big brown eyes, bangs and two, fleshy jowls on
either side of her wide grin. The mask
is the finished product of a highly precise three-dimensional facial imaging
process. For Dr. Urban, this is the face of cutis laxa, a rare disorder of the
body’s connective tissue.
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| Zsolt Urban, Ph.D. |
This weekend, the Urban lab will host patients from across
the nation for a cutis laxa clinic and information day. The clinic will allow
patients to participate in a range of clinical and research tests, including
three-dimensional facial imaging in collaboration with Seth M. Weinberg, Ph.D., of
the School of Dental Medicine. The information day will help the patients
network and learn more about cutis laxa and associated health conditions.
While the hallmark of cutis laxa is sagging skin, patients
very often have other medical conditions, since the disorder affects the
connective tissue in other parts of the body, including the heart, lungs, blood
vessels and joints. Some patients may
have difficulty breathing because the lung alveoli are not developed. Others may struggle with a variety of cardiovascular
problems, including aneurysms, vascular narrowing or stenosis.
Cutis laxa strikes roughly one in a million. There are only an
estimated 500 to 1,000 cases in the United States, but those afflicted with the
disorder may find a highly frustrating lack of information, understanding and
treatment options.
“There’s a huge problem diagnosing these patients,” said Dr.
Urban. “Most people have never heard of this condition, including a lot of
doctors. There’s no good test for it,
and it may take a long time before patients can get proper care. We are developing new techniques, such as the
three-dimensional facial imaging and skin elasticity testing for accurate and
objective diagnosis of our patients. Early diagnosis is essential. A lot of
associated health problems are age-dependent and become worse over time. Conditions like aortic aneurysms can be very
risky because there are no signs or symptoms.
Seizures can also be a problem, and they can grow worse over time.”
Researchers world-wide have identified nine genes that can
cause the disease in one baffling form or another. Dr. Urban is responsible for three of those
findings and is actively searching for novel genes using the latest DNA
sequencing technologies.
“It’s really crucial to identify the genes,” said Dr.
Urban. “If you know which gene is
mutated, then you can tailor the patient’s care.”
For example, researchers know that one specific type of
mutation will affect a patient’s heart and lungs. Another is characterized by slowed growth and
developmental delay.
At the University of Pittsburgh, Dr. Urban and his
colleagues look for the origin of the disease. The Pitt researchers examine skin cells collected from cutis laxa
patients to determine how they form the extracellular matrix, the proteins that
form the meshwork of connective tissue.
At the same time, they are actively searching for a cure. For now, they
are using zebra fish, a small freshwater fish with a well-known genome
sequence.
“We can easily inactivate the cutis laxa gene in zebra fish,”
said Dr. Urban. “We establish models of
the disorder in the fish, and then we can search for drugs that will reverse
the condition.”
Researchers have found experimental compounds that work on
cutis laxa in zebra fish, but much work remains to be done, and Dr. Urban acknowledges
that funding is a key component.
His Pittsburgh lab is developing a study of the genetic
variation in cutis laxa genes and a patient’s risk for chronic obstructive pulmonary
disorder, or COPD. Lung function is
seriously curtailed for patients with the genetic disease, as well as for the
millions of Americans currently struggling with COPD.
“Federal funding is slow for the study of rare diseases,”
Dr. Urban said. “As researchers, it’s
incumbent upon us to explain how the insights we get from these rare conditions
are broadly applicable in other disorders.”
