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Research snapshot: Potential therapeutic target for cardiomyopathy identified

New research out of the University of Minnesota Medical School shows a new potential therapeutic target for viruses causing cardiomyopathy, or disease of the heart muscle.

The paper was published in the July 2015 issue of Science Translational Medicine.

Research led by Joseph Metzger, Ph.D., looked at potential causes for cardiomyopathy, specifically related to enterovirus infection.

“We already knew enterovirus infection can cause severe cardiomyopathy,” said Metzger, chair of the Department of Integrative Biology and Physiology in the University of Minnesota Medical School. “The 2A protease is encoded by the virus and cleaves the cytoskeletal protein dystrophin. What we wanted to know was what part of the process was causing the cardiomyopathy; the loss of dystrophin or the cleaving process.”

Among the major findings in the paper:

  • The 2A protease-mediated C-terminal dystrophin cleavage fragment (CtermDys) is enough to cause marked dystrophic cardiomyopathy. When looking specifically at the heart muscle cells, cardiac stress tests showed CtermDys fragments directly caused myocardial fibrosis, higher death rates in animal models. Cardiomyopathy related to CtermDys was more severe than in hearts without dystrophin.
  • Chemical analysis indicates when CtermDys decays, dystrophin rebounds in the muscle fibers. Further testing, including looking into dystrophin replacement, shows the target balance is 50 percent membrane-bound intact dystrophin to prevent cardiomyopathy in mice.
  • Inhibiting CtermDys could stop the disease mechanisms. The research shows the CtermDys cleaved dystrophin fragment severs the critical link to cortical actin, and also inhibits the compensatory utrophin from binding at the membrane. This potential for disruption makes CtermDys a good target for potential treatments in the future.
Comments
  1. July 27, 2015 11:13 pm | cara tradisional mengobati asam urat alami Says:

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