NEW: Find great deals on the latest gadgets and more in the ScienceDaily Store!
Science News
from research organizations

Gene therapy leads to robust improvements in animal model of fatal muscle disease

January 22, 2014
University of Washington
Preclinical studies show that gene therapy can strengthen muscles and lengthen lives in animal models of a fatal congenital disease in children, X-linked myotubular myopathy. The findings demonstrate the clinical feasibility of future trials for this devastating disease. Children born with the condition have floppy muscles and breathing difficulty, and may need life support. Most die in childhood. The effectiveness of this process was tested in mice and dogs with engineered adenovirus vector carrying a gene to replace the mutation.

Dr. Martin Childers in his University of Washington office with his family pet, Bella, who carries the gene mutation for a canine disorder similar to X-linked myotubular myopathy in children.
Credit: Clare McLean/University of Washington

Preclinical studies show that gene therapy can improve muscle strength in small- and large-animal models of a fatal congenital pediatric disease known as X-linked myotubular myopathy. The results, appearing in the Jan. 22 issue of Science Translational Medicine, also demonstrate the feasibility of future clinical trials of gene therapy for this devastating disease.

Researchers, based at the University of Washington, Seattle, Washington, Généthon, France, Boston Children's Hospital in Massachusetts, and Virginia Polytechnic Institute and State University (Virginia Tech) in Blacksburg, Virginia, conducted the study. The scientists found that both mice and dogs responded from a single intravascular injection of AAV, produced at Généthon, with robust improvement in muscle strength, corrected muscle structure at the microscopic level, and prolonged life. No toxic or immune response was observed in the dogs.

These results demonstrate the efficacy of gene replacement therapy for myotubular myopathy in animal models and pave the way to a clinical trial in patients.

Children born with X-linked myotubular myopathy, which affects about 1 in 50,000 male births, have very weak skeletal muscles, causing them to appear floppy, with severe respiratory difficulties. Survival beyond birth requires intensive support, often including tube feeding and mechanical ventilation, but effective therapy is not available for patients, and most die in childhood.

Alan H. Beggs of Boston Children's Hospital, co-senior author on the paper, has studied the mutated gene, known as MTM1, for many years and previously showed that replacing missing myotubularin protein effectively improved MTM muscles' ability to contract.

Based on seminal work on local and systemic administration in a mouse model of the disease performed by Anna Buj-Bello at Généthon since 2009, Martin K. Childers, a professor of rehabilitation medicine and a regenerative medicine researcher at the University of Washington, worked with the Buj-Bello and Beggs groups.

They tested gene therapy using an engineered adenovirus vector, created by Généthon. The vector is a vehicle for delivering a replacement MTM1 gene into cells. The researchers used two animal models: mice with an engineered MTM1 mutation and dogs carrying a naturally occurring MTM1 gene mutation. These mutant animals appear very weak with shortened lifespans, similar to patients with myotubular myopathy.

"The implications of the pre-clinical findings are extraordinary for inherited muscular diseases," said Childers, co-senior author on the paper, and co-principal investigator of the study. "Two of our dogs treated with adenovirus gene therapy appear almost normal with little, if any, evidence, even microscopically, of disease caused by XLMTM."

"These results are the culmination of four years of research and show how gene therapy is effective for this genetic muscle disease," said Buj-Bello. "We finally can envision a clinical trial in patients. These are very promising results for future trials in humans. "

Robert W. Grange, Virginia Tech associate professor of human nutrition, foods and exercise, and Virginia Tech graduate student Jon Doering provided expertise to demonstrate the dramatic rescue of muscle function in the treated dogs.

"The functional improvement was truly remarkable," said Grange. "It is both incredibly exciting and humbling to contribute to such a meaningful project -- a true highlight of our careers."

Story Source:

Materials provided by University of Washington. Original written by Kim Blakeley. Note: Content may be edited for style and length.

Journal Reference:

  1. M. K. Childers, R. Joubert, K. Poulard, C. Moal, R. W. Grange, J. A. Doering, M. W. Lawlor, B. E. Rider, T. Jamet, N. Daniele, S. Martin, C. Riviere, T. Soker, C. Hammer, L. Van Wittenberghe, M. Lockard, X. Guan, M. Goddard, E. Mitchell, J. Barber, J. K. Williams, D. L. Mack, M. E. Furth, A. Vignaud, C. Masurier, F. Mavilio, P. Moullier, A. H. Beggs, A. Buj-Bello. Gene Therapy Prolongs Survival and Restores Function in Murine and Canine Models of Myotubular Myopathy. Science Translational Medicine, 2014; 6 (220): 220ra10 DOI: 10.1126/scitranslmed.3007523

Cite This Page:

University of Washington. "Gene therapy leads to robust improvements in animal model of fatal muscle disease." ScienceDaily. ScienceDaily, 22 January 2014. <>.
University of Washington. (2014, January 22). Gene therapy leads to robust improvements in animal model of fatal muscle disease. ScienceDaily. Retrieved February 26, 2017 from
University of Washington. "Gene therapy leads to robust improvements in animal model of fatal muscle disease." ScienceDaily. (accessed February 26, 2017).