Washington: Scientists have successfully tested a powerful gene therapy, delivered directly into the heart, to reverse heart failure in large animal models.
The research from the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai is the final study phase before human clinical trials can begin testing SUMO-1 gene therapy. SUMO-1 is a gene that is "missing in action" in heart failure patients.
"SUMO-1 gene therapy may be one of the first treatments that can actually shrink enlarged hearts and significantly improve a damaged heart's life-sustaining function,. We are very eager to test this gene therapy in our patients suffering from severe heart failure," the study's senior investigator Roger J. Hajjar, MD, Director of the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai and the Arthur and Janet C. Ross Professor of Medicine at Mount Sinai said.
The first trial, named CUPID, is in its final phases of testing SERCA2 gene therapy. Phase 1 and phase 2a trial results were positive, demonstrating substantial improvement in clinical events.
In that trial, a gene known as SERCA2 is delivered via an inert virus - a modified virus without infectious particles. SERCA2 is a gene that produces an enzyme critical to the proper pumping of calcium out of cells. In heart failure, SERCA2 is dysfunctional, forcing the heart to work harder and in the process, to grow larger.
The virus carrying SERCA2 is delivered through the coronary arteries into the heart during a cardiac catheterization procedure. Studies show only a one-time gene therapy dose is needed to restore healthy SERCA2a gene production of its beneficial enzyme.
In large animal models of heart failure, the researchers 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 study is published in journal Science Translational Medicine.