The first successful long-term gene therapy for neonatal hypertrophic cardiomyopathy (HCM), demonstrated in a mouse model, is reported online this week in Nature Communications. HCM is the most prevalent inherited cardiac disease, with an estimated frequency of 1 in 500.

HCM is caused by mutations in genes encoding components of the heart muscles. The disease can lead to sudden cardiac death in young adults, particularly athletes, and some patients go on to develop severe systolic dysfunction and heart failure. In newborns, HCM can rapidly evolve into systolic heart failure and death within the first year of life.

Lucie Carrier and colleagues show successful, long-term gene therapy in mice that have been engineered to genetically mimic human neonatal cardiomyopathies. A single administration of a modified virus, which delivers non-mutated genetic information into heart cells of mice, seems to prevent the symptoms of HCM from occurring during a 34 week observation period. In addition, the therapy also seems to suppress the production of mutant mRNA species, which can give rise to malformed proteins that are thought to be involved the development of the disease.

This finding, in mice, suggests that gene therapy may become a realistic treatment option for severe neonatal HCM, which is currently untreatable aside from heart transplantation. However, further trials are necessary to determine the safety and efficacy of this therapy in humans.