This means that in the next five
years we will have a working protocol that allows the damaged heart to stabilize
and prevents further deteriation. This
is important as most victims of heart attacks have lost far more heart function
that can be thought safe. Successive
attacks worsen the situation until the only escape is an actual transplant.
We are rapidly approaching the
day when a new heart on your own can be transplanted but we are not there
yet. This at least stabilizes the
disease although it does not eliminate the causes of the actual heart attacks.
Folks with moderate heart damage
and a reduced risk of a heart attack will be best placed to take advantage of
all this.
New Gene Therapy To Reverse Heart Failure Ready For Clinical Trials
A promising gene therapy developed, in part, atThomas Jefferson University’s Center for Translational Medicine to prevent and
reverse congestive heart failure is on the verge of clinical trials, after
years of proving itself highly effective in the lab and a large animal study.
Reporting in the online July 20 issue of Science Translational
Medicine, cardiology researchers have demonstrated feasibility, the long-term
therapeutic effectiveness and the safety of S100A1 gene therapy in a large
animal model of heart failure under conditions approximating a clinical
setting.
“This is the last step you have to take to finish a very long line of
research,” said Patrick Most, M.D., adjunct assistant professor of medicine
at Thomas Jefferson University, and lead author of the study who now heads the
Institute for Molecular and Translational Cardiology at the University of
Heidelberg, Germany. “The reversal of cardiac dysfunction in this
pre-clinical heart failure model in the pig by restoring S100A1 levels in
practically the same setting as in a patient is remarkable and will pave the
way for a clinical trial.”
The therapy works by raising diminished levels of the protein S100A1, a
calcium-sensing protein in the diseased heart muscle cell, to normal. Previous
research suggests this will prevent against heart failure development,
particularly in people who have had a heart attack.
According to Dr. Most, “the therapeutic profile of S100A1 is a unique
one as it targets and reverses the underlying causes of heart failure:
progressive deterioration of contractile performance, electrical instability
and energy deprivation.”
About six million people in the United States
Work on S100A1 started bench side 15 years ago with Dr. Most and Walter J Koch, Ph.D., now director of the Center for
Translational Medicine in the Department of Medicine in Jefferson Medical College of
Thomas Jefferson University, who, with his team, have moved the research closer
to bedside ever since.
Five years ago, Jefferson researchers
showed that increasing levels of the protein above normal helped protect mouse
hearts from further damage after simulated heart attacks. The hearts worked
better and had stronger contractile force.
“We have pursued a completely different path over the years,” said Dr.
Most. “We have set up a translational pipeline and don’t stick to just one
model system. We took it step by step, and did whatever was necessary to go to
the next level. We realized early on that a mouse is not a man. You need to
design target-tailored translational research strategies and work in
human-relevant model systems to take molecular discoveries from bench to bedside.
“With such a translational roadmap at hand, we are in the unique
position to accelerate future development of molecular therapies.”
In their latest study in Science Translational Medicine, Drs. Koch
and Most and their team of researchers used a pig model—this type more closely
resembles human physiology, function and anatomy—to determine the effectiveness
and safety of the S100A1 gene therapy. Researchers were also able to administer
it with certified catheters and delivery routes, just as a human patient would
receive it. “We’ve shown its effectiveness in the lab. It worked in mice and
rats, then pigs and now it’s ready for humans,” Dr Most adds.
Heart failure was induced in the pigs, and at 14 weeks showed
significantly decreased S100A1 levels. Treatment, however, with the gene
therapy prevented and reversed development of heart failure by restoring the
S100A1 protein levels or getting them above normal.
“This therapy gets to the core of the disease,” said Dr. Koch, who
received the “Outstanding Investigator Award” for 2011 by the International
Society for Heart Research for his work in heart failure gene therapy. “They
are not just beta blockers or ancillary drugs, which only block the damage.
This therapy makes the heart beats stronger and overcomes the damage from
previous heart attacks. It’s the next great thing in heart failure.”
This is the final set of preclinical data needed to apply for
investigational new drug status with the U.S.
Researchers say one of the next steps is to find industry or private
partners to help fund the work, as well as recruit eligible patients to enroll
in the clinical trial.
“With National of Institutes of Health money in jeopardy, this work
could be translated faster with funds from other sources,” said Dr. Koch. “It
could fund both ongoing research with other targets using our translational
roadmap and to take this particular target for heart failure into humans.”
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