Gene therapy reverses heart failure in pigs
Tests in mice and now pigs have shown a new targeted gene therapy can treat a major cause of heart disease. The findings suggest that the therapy, which has now passed all animal trials, could be teamed up with a different gene therapy that is already showing positive results in human trials.
The experimental therapy delivers the SUMO-1 gene into heart tissue cells using a harmless modified flu virus. Once inside the cells the gene produces a protein. This protein has been found to be lacking in some heart failure patients and was recently revealed to regulate a second protein, called SERCA2, in experiments using single cells. In further experiments, SUMO-1 gene therapy substantially improved heart function in mice with damaged hearts. SERCA2 is responsible for pumping calcium out of the cells. It is this calcium flow which creates the electrical signal that makes the heart beat. SERCA2 is already being tested as a gene therapy in human clinical trials and has so far proved safe and effective. The scientists therefore reasoned that SUMO-1 could potentially boost the power of SERCA2 therapy.
The team tested delivery of SUMO-1 gene therapy alone, SERCA2 gene therapy alone, and a combination of SUMO-1 and SERCA2 in pigs with heart failure induced by cutting off blood flow using an inflated balloon. They found that gene therapy delivery of high dose SUMO-1 alone, as well as SUMO-1 and SERCA2 together, result in stronger heart contractions, better blood flow, and reduced heart volumes, compared to just SERCA2 gene therapy alone.
The advanced stage of SERCA2 therapy could allow the team to begin human trials of their combination therapy sooner than otherwise might be the case. This is good news for the many thousands that suffer coronary heart disease. It is the UK's biggest killer, causing around 82,000 deaths each year. About one in five men and one in eight women die from the disease.