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Gene therapy may reduce risk of sudden cardiac death from heart disorder

Published: 2:44 pm CDT, June 2, 2014

A single dose of gene therapy reduced the risk of sudden cardiac death for one year from an inherited disorder that causes abnormal heart rhythm, according to a new study.

In addition, the gene therapy showed promise in preventing Catecholaminergic Polymorphic Ventricular Tachycardia from progressing after birth and in reversing it during adulthood, according to the research published in Circulation.

The effects of one dose of gene therapy lasted for one year during testing in mice, which have a similar heart anatomy to humans. The findings could have significant implications in the treatment of sudden cardiac death and inherited arrhythmia disorders for patients.

CPVT affects about one in 10,000 people worldwide and is difficult to survive, with a 50 percent mortality by 20 years old.

Exercise or stress can trigger some heart rhythm abnormalities that cause sudden cardiac arrest.

Currently, children and adults with CPVT at risk for sudden cardiac arrest are treated with beta blocker medications or atrial defibrillators to maintain normal heart rhythms.  But those treatments come with side effects and the disorder reoccurs, Treatment can be particularly difficult for children with CPVT who may struggle to endure complications.

The gene therapy tested did not produce side effects.

Lead study author Silvia G. Priori, M.D., PhD, of the Maugeri Foundation and University of Pavia in Italy, and other researchers used a deactivated virus to deliver a gene Calsequestrin 2. Patients who have CPVT have mutations or faulty changes in that gene, CASQ2, and that causes a cascade of reactions, including abnormal heart cell communication and structural problems with the heart.

The researchers conducted two sets of experiments. The first one looked at delivering the gene therapy to infant mice with the severe form of CPVT, similar to what humans experience, and then following their progress at three, six, and nine months after birth. The second study looked at delivering the gene therapy to adult mice with full-blown CPVT. Researchers also studied the animals’ heart rhythm and structure to identify any changes.

The infant mice were cured of CPVT for one year after a single dose. The gene therapy prevented both abnormal development of the heart structure as the animal grew as well as abnormal heart rhythms. A single dose made a huge impact on adult mice with severe forms of CPVT. Those curative effects also lasted one year.

“The most surprising finding was to see that the gene therapy was able to reverse the disease in animals that are adult and had already developed severe arrhythmias,” said Dr. Priori. “This opens to the possibility of treating all patients, even when diagnosis is made later in life.”

Whether this approach would work year after year is not yet known.

In an accompany editorial in Circulation, researchers from New York and London, not affiliated with the study, noted the great need for more targeted CPVT treatments that cause fewer side effects. They praised the findings while cautioning that more research is needed before such studies could include patients.

The editorial noted that what worked in this study would need to be repeated several times to truly confirm the gene therapy’s potential.