INDIANAPOLIS—With a five-year, $3.8 million grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH), Indiana University School of Medicine researchers will investigate the effects of muscle-directed gene therapies and test alternative treatment options for degenerative disorders such as Duchenne muscular dystrophy (DMD).
Duchenne muscular dystrophy is an inherited disorder characterized by progressive muscle loss that primarily affects young males. Current treatments for DMD involve using adeno-associated virus (AAV) to deliver treated genes by injections directly into the muscle or bloodstream to reach different muscles in the body.
“Gene therapies for conditions like Duchenne muscular dystrophy have been developed, but they come with adverse side effects and may show diminishing effectiveness over time,” said Roland Herzog, PhD, Riley Children's Foundation Professor of Immunology for IU School of Medicine Department of Pediatrics. “With our new NIH grant, we can gain a deeper understanding of how the immune system responds to these treatments so we can develop more successful and long-term ways to help patients living with muscle disorders.”
Herzog will lead the project, called “Mechanism of immune response to muscle-directed AAV gene transfer,” with co-investigator Dongsheng Duan, PhD, Margaret Proctor Mulligan Professor in Medical Research at the University of Missouri School of Medicine.
Their research aims to understand how the body’s initial immune response in AAV muscle gene transfer can lead to a longer and more targeted response, find ways to prevent the immune system from attacking treated muscles and develop novel protocols for re-administering AAV delivery in future patients.
“The immune response is a major barrier in AAV-mediated muscle gene therapy,” said Duan. “The new study will shed critical light on the underlying mechanisms and lead to improved gene therapy for patients suffering from muscular dystrophies.”
Herzog and Duran along with IU researcher Sandeep Kumar, MS, PhD, recently published an article in Human Gene Therapy about the serious concerns noted in clinical observations from muscle-directed gene therapy using AAV vectors.
“It’s an especially noteworthy time for DMD gene therapies as companies trying to get their treatments on the market face extra scrutiny from scientists and the U.S. Food and Drug Administration,” said Herzog. “A major reason for the ongoing controversial discussion about how safe these therapies are is the potential for serious and life-threatening immune responses and toxicities. Our goal is to make gene therapies safer and more effective.”
As director of the gene and cell therapy research program at the Herman B Wells Center for Pediatric Research, Herzog leads a group dedicated to improving current treatments, developing corrective therapies and exploring new technologies to address genetic disease. Additional information about the gene and cell therapy research group can be found on their website.
The research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI177600. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About IU School of Medicine
IU School of Medicine is the largest medical school in the United States and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.
Human Gene Therapy
Immune Responses to Muscle-Directed Adeno-Associated Viral Gene Transfer in Clinical Studies
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