Stanford Medicine

Allele silencing

Hypertrophic Cardiomyopathy is the most common inherited cardiac disease, affecting one in five hundred people worldwide. It is caused in each patient by a mutation, usually single base pair changes, in any one of a number of genes encoding cardiomyocyte specific proteins. Patients with hypertrophic cardiomyopathy (HCM) can be without symptoms, or can develop symptoms of lightheadedness, chest pain, shortness of breath, and exercise intolerance. In addition, patients can be at increased risk for sudden cardiac death. Current treatments focus on symptom and risk management, but do not attack the root cause of the disease, which is the underlying mutation. We are using a natural defense mechanism, RNA silencing (RNAi), to target individual, single base pair mutations in cell and model systems. We hope that this technology will allow us to individualize therapy for this disease, as affected members of one family share a mutation that is often unique to their family. We are developing, in parallel, methods for efficient transfer of RNAi to specifically target genes involved in the pathogenesis of HCM. Our goal is to show in preclinical models that we can ameliorate the functional consequences of HCM mutations through the use of targeted RNAi.

This work is funded by the NIH Director's New Innovator Award.