Gene therapy can be used to treat patients who have suffered damage to their hearts following cardiac arrests and other heart conditions, a new study by American researchers reveals.
The research group was led by University of Washington (UW) Professor and Vice Chair of Bioengineering Michael Regnier and Dr. Chuck Murry, director of the Center for Cardiovascular Biology and co-director of the Institute for Stem Cell and Regenerative Medicine at UW.
Normally, muscle contraction is powered by a molecule, the nucleotide called Adenosine-5'-triphosphate (ATP).
In a previous study of isolated muscle, Regnier, Murry and colleagues had found that one naturally occurring molecule, called 2 deoxy-ATP (dATP), was actually more effective than ATP in boosting muscle contraction, increasing both the speed and force of the contraction, at least over the short-term.
In the new study, the researchers wanted to see if this effect could be sustained. For this, they used genetic engineering to create a strain of mice whose cells produced higher-than-normal levels of an enzyme called Ribonucleotide Reductase that converts the precursor of ATP, adenosine-5'-diphosphate or ADP, to dADP, which, in turn, is rapidly converted to dATP.
The researchers found that increased production of the enzyme Ribonucleotide Reductase increased the concentration of dATP within heart cells approximately tenfold, and even though this level was still less than one to two percent of the cell's total pool of ATP, the increase led to a sustained improvement in heart muscle function, with the genetically engineered hearts contracting more quickly and with greater force.
"The same pathway that heart cells use to make the building blocks for DNA during embryonic growth makes dATP to supercharge contraction when the adult heart is mechanically stressed," Murry said.
Importantly, the elevated dATP effect was achieved without imposing additional metabolic demands on the cells, suggesting the modification would not harm the cell's functioning over the long-term.
The findings suggest that treatments that elevate dATP levels in heart cells may prove to be an effective treatment for heart failure.
The study has been published in the journal Proceedings of the National Academy of Sciences (PNAS).