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Enzyme Replacement Therapy Shows Promise at Medical College

Mice respond well to treatment for missing enzyme in rare and fatal muscle disorder, and hope is on a nearer horizon for children as a result.

Once again, researchers at the Medical College of Wisconsin are proving that the Wauwatosa institution is on the cutting edge of cures and treatment for rare genetic diseases – but with findings that could have implications for many more human ailments.

A collaborative research team including a Medical College pediatric neuropathologist successfully mitigated some of the effects of a muscular disease by using a new targeted enzyme replacement therapy strategy.

The findings are published in the January edition of Human and Molecular Genetics.

The tongue-twisting condition researchers looked at – "X-linked myotubular myopathy" (XLMTM) – is a severe muscle disease caused by an absence of a protein called myotubularin. There is currently no treatment for this disorder, and most patients die in infancy or childhood. The overall incidence of myotubular myopathy is 1 in 50,000 live male births.

Michael W. Lawlor coordinated a study at Boston Children’s Hospital and MCW that used targeted enzyme replacement therapy developed by 4s3 Bioscience to deliver myotubularin to muscles of mice with XLMTM. After two weeks of treatment, the mice showed marked improvement in muscle function and pathology.

“These promising findings suggest that even low levels of myotubularin protein replacement can not only improve weakness in patients, but also at least partially reverse the structural abnormalities seen in XLMTM,” Lawlor said. “The next step is to determine appropriate dosage, and toxicity, before we venture into human trials."

As studies progress, Lawlor will continue to perform pathological analyses on research tissue from preclinical studies with the 4s3 Bioscience replacement enzyme and assist in further elucidating the pathophysiology of XLMTM.  This work by Dr. Lawlor’s laboratory utilizes resources partially supported and available through the Children’s Research Institute’s Imaging Core Facility.

The study was supported by the National Institutes of Health, the Muscular Dystrophy Association, the Joshua Frase Foundation, and the Lee and Penny Anderson Family Foundation.

Lawlor, M.D., Ph.D., is an assistant professor of pathology at MCW, a researcher at the Children’s Hospital of Wisconsin Research Institute, and director of the pediatric pathology neuromuscular laboratory in MCW’s division of pediatric pathology.

Co-authors of the study are Dustin Armstrong and Michael O’Callaghan from 4s3 Bioscience, Inc.; Marissa Viola, Cynthia P. Hsu, and Alan H. Beggs from Boston Children’s Hospital and Harvard Medical School; Jeffrey J. Widrick from Spaulding Rehabilitation Hospital; Hui Meng from MCW; Robert W. Grange from Virginia Tech; Martin Childers from Wake Forest University; Christopher R. Pierson from Nationwide Children’s Hospital; and Anna Buj-Bello from INSERM. 

The efforts of Drs. Armstrong, Beggs, and Lawlor began while Dr. Lawlor was working for Dr. Beggs at Boston Children’s Hospital, and this collaborative effort has continued at Dr. Lawlor’s lab at MCW.

About the Medical College of Wisconsin

The Medical College of Wisconsin is the state’s only private medical school and health sciences graduate school. Founded in 1893, it is dedicated to leadership and excellence in education, patient care, research and service. More than 1,200 students are enrolled in the Medical College’s medical school and graduate school programs.  A major national research center, it is the largest research institution in the Milwaukee metro area and second largest in Wisconsin. In FY 2010 – 11, faculty received more than $175 million in external support for research, teaching, training and related purposes, of which more than $161 million is for research. This total includes highly competitive research and training awards from the National Institutes of Health (NIH).  Annually, College faculty direct or collaborate on more than 2,200 research studies, including clinical trials. Additionally, more than 1,350 physicians provide care in virtually every specialty of medicine for more than 400,000 patients annually.

 

About Children’s Hospital of Wisconsin

Children’s Hospital of Wisconsin is the region’s only independent health care system dedicated solely to the health and well-being of children. The hospital, with locations in Milwaukee and Neenah, Wis. is recognized as one of the leading pediatric health care centers in the United States. Children’s Hospital provides primary care, specialty care, urgent care, emergency care, community health services, foster and adoption services, child and family counseling, child advocacy services and family resource centers. In 2011, Children’s Hospital invested more than $100 million in the community to improve the health status of children through medical care, advocacy, education and pediatric medical research. Children’s Hospital achieves its mission in part through donations from individuals, corporations and foundations and is proud to be a Children’s Miracle Network Hospital. For more information, visit the website at chw.org.

 

About Children’s Hospital of Wisconsin's Research Institute

Children's Research Institute is the only entity of its kind in the region advancing pediatric medical research for children in Wisconsin and beyond and is a member of Children’s Hospital of Wisconsin, the region’s only independent health care system dedicated solely to the health and well-being of children. The hospital, with locations in Milwaukee and Neenah, Wis. is recognized as one of the leading pediatric health care centers in the United States. Children’s Hospital provides primary care, specialty care, urgent care, emergency care, community health services, foster and adoption services, child and family counseling, child advocacy services and family resource centers. In 2011, Children’s Hospital invested more than $100 million in the community to improve the health status of children through medical care, advocacy, education and pediatric medical research. Children’s Hospital achieves its mission in part through donations from individuals, corporations and foundations and is proud to be a Children’s Miracle Network Hospital. For more information, visit the website at chw.org.

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