Gene therapy of heart failure
In experiments on a large animal model, researchers at Mount Sinai Clinic, working under the guidance of Professor Roger J. Hajjar, successfully tested an experimental gene therapy that delivers the therapeutic gene SUMO-1 directly into the cardiomyocytes of patients with heart failure.
Heart failure is the leading cause of hospitalization of the elderly, claiming about 300,000 lives annually in the United States alone. Heart failure develops in cases when a person's heart does not contract strongly enough and cannot provide normal blood circulation in the body.
The US Food and Drug Administration (FDA) is already considering an application for clinical trials of SUMO-1 gene therapy involving patients with heart failure. Earlier, Dr. Hajjar had already received permission to conduct a clinical study of gene therapy of heart failure using the SERCA2a gene. This study, dubbed CUPID, is already nearing completion. Phases 1 and 2a of the study have yielded promising results.
As part of the CUPID study, an adenoviral carrier vector was injected into the coronary artery of patients delivering the SERCA2a gene to heart cells, the protein product of which is an enzyme necessary for the effective pumping of calcium ions from the cell. In heart failure, this protein does not perform its function, which causes the heart to contract more and leads to its hypertrophy. According to the results obtained, a single administration of a gene therapy drug is sufficient to restore normal production of the enzyme encoded by the SERCA2a gene.
However, in earlier studies, the authors found that SERCA2a is not the only protein whose activity is reduced in heart failure. This disease is also characterized by low activity of the protein SUMO-1, which regulates the activity of SERCA2a. Based on this, they suggested that increasing the activity of SUMO-1 would increase the functionality of SERCA2a without changing its concentration in the cell. Experiments on mice have demonstrated that gene therapy using the SUMO-1 gene significantly improves cardiac function in the treatment of simulated heart failure.
Adenovirus vectors injected into the coronary artery,
the SUMO-1 gene is delivered to the cells of a sick heart,
increasing the activity of SERCA2aIn the latest work, the authors compared the effectiveness of three gene therapy variants on a pig model of heart failure: SUMO-1, SERCA2 and a combination of these two genes.
The obtained results showed that in relation to such indicators as the strength of heart contractions, the efficiency of blood supply and a decrease in heart volume, therapy with high doses of the SUMO-1 gene and a combination of the SUMO-1 and SERCA2a genes provides more pronounced improvements than therapy with the SERCA2a gene.
According to Dr. Hajjar, the transition from an interesting laboratory finding to the successful completion of preclinical studies was completed in record time. Now the researchers are hoping to quickly obtain FDA approval to conduct clinical trials.
Article by L. Tilemann et al. Gene Transfer Improves Cardiac Function in a Large-Animal Model of Heart Failure published in the journal Science Translational Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on materials from Mount Sinai Medical Center, via Newswise:
Novel Gene Therapy Works to Reverse Heart Failure.
15.11.2013