New research in the FASEB Journal shows that fast myosin
motor gene transfer increases contractions of heart muscle cells
Scientists from the Universities of Michigan and Minnesota show in a
research report published online in the FASEB Journal (http://www.fasebj.org) that gene therapy may
be used to improve an ailing heart's ability to contract properly. In addition
to showing gene therapy's potential for reversing the course of heart failure,
it also offers a tantalizing glimpse of a day when "closed heart
surgery" via gene therapy is as commonly prescribed as today's cocktail of
drugs.
"We hope that our study will lead some day to the
development of new genetic-based therapies for heart failure patients,"
said Todd J. Herron, Ph.D., one of the researchers involved in the study and
research assistant professor of molecular and integrative physiology at the University of Michigan. "The advent of molecular
motor-based gene transfer for the failing heart will hopefully improve cardiac
function and quality of life for heart failure patients."
To make this advance, Herron and colleagues treated heart
muscle cells from the failing hearts of rabbits and humans with a virus
(adenovirus) modified to carry a gene which produces a protein that enables
heart cells to contract normally (fast molecular motor) or a gene that becomes
active in failing hearts, which is believed to be part of the body's way of
coping with its perilous situation (slow molecular motor). Heart cells treated with
the gene to express the fast molecular motor contracted better, while those
treated with the gene to express the slow molecular motor were unaffected.
"Helping hearts heal themselves, rather than
prescribing yet another drug to sustain a failing organ, would be a major
advance for doctors and patients alike," said Gerald Weissmann, M.D.,
Editor-in-Chief of the FASEB Journal. "Equally important, it shows that
gene therapy remains one of the most promising approaches to treating the
world's most common and deadliest diseases."
According to the U.S. Centers for Disease Control and
Prevention, heart failure is a condition where the heart cannot pump enough
blood and oxygen to meet the needs of other body organs. Approximately 5
million people in the United States
have heart failure, about 550,000 new cases are diagnosed each year, and more
than 287,000 people in the United
States die each year of heart failure. The
most common causes of heart failure are coronary artery disease, hypertension
or high blood pressure, and diabetes. Current treatments usually involve three
to four medicines: ACE inhibitors, diuretics, digoxin, and beta blockers.
Current clinical agents and treatments focus on the amount
of calcium available for contraction, which can provide short-term cardiac
benefits, but are associated with an increased mortality in the long-term.
Results from this study show that calcium-independent treatments could have
implications for heart diseases associated with depressed heart function, due
to the effectiveness of fast molecular motor gene transfer on the improved
contractions of human heart muscle cells.
Details: Todd J. Herron, Eric Devaney, Lakshmi Mundada, Erik
Arden, Sharlene Day, Guadalupe Guerrero-Serna, Immanuel Turner, Margaret
Westfall, and Joseph M. Metzger. Ca2+-independent positive molecular inotropy
for failing rabbit and human cardiac muscle by alpha-myosin motor gene
transfer. FASEB J. doi:10.1096/fj.09-140566 ; http://www.fasebj.org/cgi/content/abstract/fj.09-140566v1
Federation of American
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