Features Partner Sites Information LinkXpress
Sign In
Demo Company

Novel Gene Therapy Works to Reverse Heart Failure

By BiotechDaily International staff writers
Posted on 26 Nov 2013
Print article
Image: AAV vectors are delivered through the coronary arteries of the failing heart delivering SUMO1, which in turns enhances the activity of SERCA2a (Photo courtesy of Mount Sinai Hospital).
Image: AAV vectors are delivered through the coronary arteries of the failing heart delivering SUMO1, which in turns enhances the activity of SERCA2a (Photo courtesy of Mount Sinai Hospital).
Researchers have effectively evaluated a powerful gene therapy, delivered directly into the heart, designed to reverse heart failure in large animal models. Only a one-time gene therapy dose was found to be needed to restore healthy gene production of a beneficial enzyme.

Published in November 13, 2013, issue of the journal Science Translational Medicine, the study findings, is the last study phase before human clinical trials can start assessing SUMO-1 (small ubiquitin-related modifier) gene therapy. SUMO-1 is a gene that is absent 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,” stated the study’s senior investigator Roger J. Hajjar, M.D., director of the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai (New York, NY, USA) and a professor of medicine at Mount Sinai. “We are very eager to test this gene therapy in our patients suffering from severe heart failure.”

Dr. Hajjar’s work is on its way toward approval from the US Food and Drug Administration (FDA) to evaluate the SUMO-1 gene therapy in heart failure patients. When it begins, the clinical trial will be the second gene therapy treatment designed to reverse heart failure launched by Dr. Hajjar and his Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai.

The first trial, named CUPID, is in its final phases of testing SERCA2 gene therapy. Adeno-associated virus (AAV) vectors are delivered through the coronary arteries of the failing heart during a cardiac catheterization procedure, delivering SUMO1, which then enhances the activity of a gene known as SERCA2a (sarcoplasmic reticulum calcium ATPase 2a). Phase 1 and phase 2a trial findings were positive, demonstrating considerable improvement in clinical events. In that trial, SERCA2 is delivered by way of an inert virus--a modified virus without infectious particles. SERCA2 is a gene that produces an enzyme vital to the effective 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.

Earlier research, however, by Mount Sinai scientists demonstrated SERCA2 is not the only enzyme that is missing in heart failure processes. A study published in the journal Nature in 2011 by Dr. Hajjar and his coworkers revealed that the SUMO-1 gene is also reduced in failing human hearts. But SUMO-1 controls SERCA2a’s activity, suggesting that it can enhance the function of SERCA2a without changing its levels. A follow-up study in a mouse model of heart failure demonstrated that SUMO-1 gene therapy substantially improved cardiac function.

This new study evaluated delivery of SUMO-1 gene therapy alone, SERCA2 gene therapy alone, and a combination of SUMO-1 and SERCA2. 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 better blood flow, stronger heart contractions, and reduced heart volumes, compared to just SERCA2 gene therapy by itself. “These new study findings support the critical role SUMO-1 plays for SERCA2 function, and underlie the therapeutic potential of SUMO-1 gene replacement therapy for heart failure patients,” reported Dr. Hajjar.

Furthermore, according to Dr. Hajjar, the time it took investigators to convert their basic laboratory findings to successful preclinical studies was very short. “The key reason for this translational medicine speed is the outstanding infrastructure we have in the Cardiovascular Research Center at Mount Sinai, where we are able to replicate human heart failure models to test our novel gene therapies,” noted Dr. Hajjar. “I think this is a really very unique example of rapid translation of a promising medical therapy from an initial discovery to preclinical trials.”

Dr. Hajjar is the scientific cofounder of the company Celladon (San Diego, CA, USA), which plans to develop AAV.SERCA2a gene therapy for the treatment of heart failure.

Related Links:

Mount Sinai

Print article



view channel
Image: Sequencing and analysis of the pineapple genome offers new insights into the evolution of plant drought-resistance, different types of photosynthesis, and circadian clock regulatory adaptations (Photo courtesy of Robert E. Paull, University of Hawaii).

Insights into Evolution of Drought-Tolerance Revealed by Pineapple Genome

Upon sequencing its genome, scientists begin to home in on genes and pathways that enable the pineapple plant to thrive in water-limited environments and open a new window on CAM photosynthesis, circadian... Read more


view channel
Image: A partially completed three-dimensional printed airway from nostril to trachea with fine structure of the nasal cavity showing (Photo courtesy of Dr. Rui Ni, Pennsylvania State University).

The Structure of the Nasal Cavity Channels Food Smells into the Nose and Avoids the Lungs

Three-dimensional printing technology was used to create a model of the nasal cavity that enabled researchers to demonstrate why the smell of food goes into the nose rather than down into the lungs.... Read more

Lab Technologies

view channel
Image:  The BioSpa 8 Automated Incubator (Photo courtesy of BioTek Instruments).

Smart Incubator System Automates Live Cell Assay Operations

A new instrument that automates laboratory workflow by linking microplate washers and dispensers with readers and imaging systems is now available for biotech and other life sciences researchers.... Read more


view channel

Purchase of Biopharmaceutical Company Will Boost Development of Nitroxyl-Based Cardiovascular Disease Drugs

A major international biopharmaceutical company has announced the acquisition of a private biotech company that specializes in the development of drugs for treatment of cardiovascular disease. Bristol-Myers Squibb Co. (New York, NY, USA) has initiated the process to buy Cardioxyl Pharmaceuticals Inc. (Chapel Hill, NC, USA).... Read more
Copyright © 2000-2015 Globetech Media. All rights reserved.