Gene therapy may aid failing hearts

March 26, 2013

In an animal study, researchers at the University of Washington show that it was possible to use gene therapy to boost heart muscle function. The finding suggests that it might be possible to use this approach to treat patients whose hearts have been weakened by heart attacks and other heart conditions.

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, the study appears online today in the journal Proceedings of the National Academy of Sciences (PNAS).

Normally, is powered by a molecule, the nucleotide called Adenosine-5'-triphosphate (ATP). Other naturally occurring nucleotides can also power muscle contraction, but, in most cases, they have proven to be less effective than ATP.

In an earlier study of isolated muscle, however, Regnier, Murry and colleagues had found that one naturally occurring molecule, called 2 deoxy-ATP (dATP), was actually more effective than ATP in powering muscle contraction, increasing both the speed and force of the contraction, at least over the short-term.

In the new PNAS study, the researchers wanted to see whether this effect could be sustained. To do this, they used genetic engineering to create a strain of mice whose cells produced higher-than-normal levels of an enzyme called Ribonucleotide Reductase, which converts the precursor of ATP, adenosine-5'- or ADP, to dADP, which, in turn, is rapidly converted to dATP.

"This fundamental discovery, that dATP can act as a 'super-fuel' for the contractile machinery of the heart, or myofilaments, opens up the possibility to treat a variety of heart failure conditions," Regnier said. "An exciting aspect of this study and our ongoing work is that a relatively small increase in dATP in the has a big effect on heart performance."

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 function, with the genetically engineered hearts contracting more quickly and with greater force.

"It looks as though we may have stumbled on an important pathway that nature uses to regulate heart contractility," Murry added. "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."

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 finding, the authors write, suggest that treatments that elevate dATP levels in heart cells may prove to be an effective treatment for .

Explore further: Depressed heart function from stress improved by a simple sugar

Related Stories

Depressed heart function from stress improved by a simple sugar

July 19, 2011
Enhancing the production of ATP (adenosine triphosphate), an energy carrying molecule in heart cells, may shorten the heart’s recovery time after a heart attack or heart surgery.

Heart failure's effects in cells can be reversed with a rest

April 2, 2012
Structural changes in heart muscle cells after heart failure can be reversed by allowing the heart to rest, according to research at Imperial College London. Findings from a study in rats published today in the European Journal ...

Heart muscle cell grafts suppress arrhythmias after heart attacks in animal study

August 5, 2012
Researchers have made a major advance in efforts to regenerate damaged hearts.

Recommended for you

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

DavidW
1 / 5 (1) Mar 26, 2013
"The finding suggests that it might be possible to use this approach to treat patients whose hearts have been weakened by heart attacks and other heart conditions."

Meanwhile, eating a vegan diet is seen and recognized as the the very best way to prevent and treat heart disease.

Man - "I will ignore all commonsense if it means I get to kill and harm other life for my own personal gratification."

That's a sickness.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.