CONTACT: JENNIFER CRONIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-9917; fax (319) 335-8034
Release: Aug. 19, 1999
UI study identifies mechanism that causes cardiomyopathy,
exacerbates muscular dystrophy
IOWA CITY, Iowa Results from a University of
Iowa Health Care study may help researchers to better understand and find
ways to treat heart problems related to a certain type of muscular dystrophy.
In an article appearing in the Aug. 20 issue of the
journal Cell, UI researchers outline, for the first time, a complex domino
effect that ultimately leads to a type of heart disease known as cardiomyopathy,
which exacerbates limb-girdle muscular dystrophy (LGMD).
"Our results have important implications for scientists
developing gene therapy for limb-girdle muscular dystrophy and for neurologists
who treat muscular dystrophy patients with cardiomyopathy," said Kevin Campbell,
Ph.D., UI professor physiology and biophysics, and neurology, and a Howard
Hughes Medical Institute (HHMI) investigator. "Our results suggest that drug
therapy directed toward vascular smooth muscle could be effective in preventing
and/or stabilizing cardiomyopathy in some cases of muscular dystrophy."
Campbell has focused much of his career on understanding
and trying to find ways to treat the various forms of muscular dystrophy,
a group of hereditary diseases characterized by progressive muscle weakness
and degeneration. LGMD, which affects between one in 20,000 and one in 50,000
individuals, involves initial deterioration of shoulder and pelvic girdle
muscles, with relative sparing of other muscle groups. Although various studies
of patients with LGMD have shown eventual cardiac involvement, no one had
ever established a correlation between the genetic mutation that causes LGMD
Based on his previous work, Campbell knew that genetic
flaws in muscle cell proteins known as sarcoglycans caused LGMD. Sarcoglycans
are a substructure of the bigger dystrophin-glycoprotein complex, which researchers
believe protects muscle cells from contraction-induced damage.
Using genetically engineered mice, Campbell and his
research team showed that those animals lacking a type of sarcoglycan, identified
as the delta subunit, experienced severe muscular dystrophy with large areas
of cardiac cell death. Campbell and other researchers in his lab determined
that this disruption in the sarcoglycan complex upsets vascular function and
causes injury in cardiac and skeletal muscles. This injury leads to cardiac
complications, which exacerbate LGMD.
"A number of proteins in cardiac muscle have been
shown to be involved in cardiomyopathy," Campbell said. "However, our study
opens up a unique and important new avenue of research directed toward the
involvement of the vascular smooth muscle sarcoglycan-sarcospan complex in
the cause and progression of cardiomyopathy."
Now that Campbells lab has identified the problem
that leads to cardiomyopathy in patients with LGMD, the next step is to look
at possible pharmacological treatments to prevent vascular smooth muscle dysfunction.
Campbell also wants to investigate gene transfer as a way to repair the sarcoglycan
complex in vascular smooth muscles and develop additional animal models to
evaluate smooth muscle contributions to cardiomyopathy.
In addition to Campbell, the other two primary investigators
of this most recent study included postdoctoral associates Ramon Coral-Vazquez,
Ph.D., and Ronald D. Cohn, M.D., both members of Campbells HHMI lab
team. Other UI collaborators included Joseph A. Hill, M.D., Ph.D., assistant
professor of internal medicine; Robert M. Weiss, M.D., associate professor
of internal medicine; Robin Davisson, Ph.D., assistant professor of anatomy
and cell biology; Steve Moore, M.D., Ph.D., professor of pathology; and Roger
Williamson, M.D., professor of obstetrics and gynecology.
In addition to support from the HHMI, the Muscular
Dystrophy Association also funded this research.
NOTE TO EDITORS: To arrange an interview with Kevin
Campbell, contact Jennifer Cronin at (319) 335-9917.