Gene Therapy for Treating Heart Failure

Heart failure (HF) in the presence of systolic dysfunction and reduced ventricular ejection fraction (a measure of the heart's pumping capacity) is a disease with many causes. Physicians must prescribe a combination of drugs to optimally treat the disease. Many medications used to treat HF work by blocking neurohormonal systems activated in the presence of a failing heart. Commonly used drugs include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, diuretics, and aldosterone receptor antagonists. Standard regimens of neurohormonal-blocking drugs have been shown to reduce mortality, morbidity, and hospitalization in patients with HF. In addition, these drugs can often improve a patient's functional abilities and quality of life.1 However, current treatments are seldom able to reverse the disease process, and mortality from the disease remains high, even when optimally treated.2

Research suggests that defects in certain genes could contribute to the onset and progression of HF by reducing production of proteins known to regulate heart contractility. Therefore, some researchers propose that gene therapies could be used to correct or replace faulty genes, restore levels of key proteins, and help restore the heart's pumping capacity. In addition, some researchers believe that these gene therapies might be able to reverse the disease process in some patients. Gene therapy is currently being evaluated as an adjunct to standard therapy in patients with reduced-ventricular ejection fraction HF.3 Experts suggest that patients with normal-ejection fraction HF are not likely to benefit from this therapy.4

Celladon Corporation (La Jolla, CA, USA) is developing MYDICAR, a genetically targeted enzyme replacement therapy to treat HF. MYDICAR uses an adeno-associated virus (AAV) vector to deliver the genetic material into cells. MYDICAR is intended to restore levels of Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA) 2a, an enzyme that helps regulate calcium cycling in cardiac muscle cells. Physicians deliver MYDICAR to the heart via a single catheter-based infusion into the coronary arteries during an outpatient procedure in a cardiac catheterization laboratory. Celladon licensed the AAV vector technology from AmpliPhi...