Heart researchers at the Center for Translational Medicine at Jefferson Medical College led by Walter J. Koch, Ph.D., have used gene therapy to reverse heart failure in animals. In addition, they found that this gene therapy strategy had “unique and additive effects” to currently used, standard heart failure drugs called beta-blockers.
The team of scientists used a virus to carry the gene for a protein, S100A1, into the heart cells of rats with heart failure. The virus expressed the S100A1 gene only in heart cells and not in other organs, essentially making it a tailored therapy. After 18 weeks, those animals that received the gene therapy had significantly improved heart function compared to animals that did not receive the treatment.
S100A1, part of a larger family of proteins called S100, is primarily found at high levels in muscle, particularly the heart. Falling levels of S100A1 are critical in the loss of heart-pumping strength after a heart attack and play an important role in the progression to heart failure. Previous studies by other researchers showed that the protein was reduced by as much as 50 percent in patients with heart failure.
The rats with heart failure were then followed for another two months, when their heart pumping function was monitored again. The animals that received the gene therapy had significantly better heart-pumping abilities compared to the pre-gene therapy level, and overall, the S100A1-treated rats had improved heart health. The researchers found this in both individual heart cells and in the whole animal as well.
The researchers also discovered that the S100A1 gene therapy changed the geometry of the heart. In heart failure, the heart tends to increase in size. The added S100A1 slowed down this process and actually reversed it.
According to Dr. Koch the added S100A1 appears to improve calcium signaling in heart cells, which is critical to the force of contraction of individual cells.
In another arm of the study, the scientists looked at the effects of beta-blockers alone or in combination with the S100A1 gene therapy. They found that beta-blockers only partially rescued the animals’ hearts in failure and that S100A1 gene therapy alone was significantly better at improving heart function in the model. “Importantly, the combination of the two was also therapeutic and in some indices studied there were additive effects,” Dr. Koch notes. “However, it should be stressed that the beta-blocker could stop progression of heart failure in this model. S100A1 gene therapy not only stopped progression but reversed damage and actually improved the heart’s performance.”
Congestive heart failure affects nearly five million Americans, many of whom have poor long-term prognoses, despite recent therapeutic advances.
Illustration: MicroSoft clipart.
Thomas Jefferson University (05/23/07)
Huliq Breaking News (05/24/07)
Science Daily (05/24/07)
Times of India (05/25/07)
Medical News Today (05/29/07)