“We are very encouraged by the ability of gene delivered follistatin to increase muscle mass and strength along with a relatively clean safety profile in our studies to date,” say Drs. Jerry Mendell and Brian Kaspar of The Research Institute at Nationwide Children’s Hospital. “While the first trials of follistatin are planned for Becker Muscular Dystrophy and Inclusion Body Mysositis, if proven safe and efficacious, Spinal Muscular Atrophy patients may also benefit from this treatment.” Work in the Kaspar Laboratory is currently testing gene delivered Follistatin in various SMA models.

From Nationwide Children’s Hospital:

Parent Project Muscular Dystrophy Awards $600K to Nationwide Children’s Hospital for Gene Therapy Study

Dr. Jerry Mendell Leading Follistatin Gene Therapy

Columbus, OH – 8/10/2010

Parent Project Muscular Dystrophy (PPMD), the largest non-profit organization in the United States focused on finding a cure for Duchenne muscular dystrophy (Duchenne), announced that PPMD will award a $600,000 grant to Nationwide Children’s Hospital in Columbus, Ohio to conduct clinical testing of a promising gene therapy technique for muscle disease.

Investigators, led by Jerry Mendell, M.D., director of the Center for Gene Therapy in The Research Institute at Nationwide Children’s Hospital with co-investigator Brian Kaspar, Ph.D, will inject a modified virus (vector) carrying the gene for the muscle growth-stimulating protein follistatin into the quadriceps muscles of volunteers with Becker muscular dystrophy and sporadic inclusion body myositis. The goal of the study is to verify that the procedure is safe and to document any increase in quadriceps muscle size and function. People with these diseases have overall muscle weakness but with particular weakness of the quadriceps muscle, which is important for standing and sitting. Preliminary studies in mice with muscular dystrophy and in non-human primates demonstrated that follistatin delivered in this manner can cause significant increases in the size of injected muscles. Improvements in the strength of the mice and non-human primates were documented.

PPMD funding for the project will cover the costs of manufacturing the clinical grade viral vectors, and the costs associated with the clinical testing. If the initial study is successful, the investigators will expand the research to a phase II study and will also make plans to test it in Duchenne muscular dystrophy and other muscle diseases. The first clinical studies are planned to start in early 2011.

“This is the first time a gene therapy approach has been used to supply genes that generically stimulate muscle growth rather than directly replacing missing muscle proteins,” explains Sharon Hesterlee, Ph.D., PPMD Senior Director of Research and Advocacy, “Other applications could include the treatment of muscles that have been injured directly through accidents or indirectly through disuse.”

To read the rest of the announcement, click here.

From Nationwide Children’s Hospital:

Spinal Muscular Atrophy May Also Affect the Heart

Study details new findings in mouse model of disease; highlights existing gene delivery approach that may provide therapy

Columbus, OH – 8/11/2010

Along with skeletal muscles, it may be important to monitor heart function in patients with spinal muscular atrophy (SMA). These are the findings from a study conducted by Nationwide Children’s Hospital and published online ahead of print in Human Molecular Genetics. This is the first study to report cardiac dysfunction in mouse models of SMA.

SMA is a debilitating neurological disease that leads to wasting away of muscles throughout the body. Historically, scientists and physicians believed that SMA only affected skeletal muscles; however, new data suggests that this genetic disease may also impact the heart.

“A few studies regarding SMA patients have implicated the involvement of the cardiovascular and the autonomic nervous system,” said the study’s co-author Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital. “However, there have been few to no highly powered and controlled studies to determine how common these cardiovascular anomalies are in these patients.”

The reports of altered blood flow and slowed heart rate in some SMA patients prompted Kaspar’s team to examine whether a cardiac deficit is present in a mouse model of severe SMA, developed by Arthur Burghes, PhD, professor of Molecular and Cellular Biochemistry at The Ohio State University College of Medicine, which is routinely used for drug and therapeutic-based screening.

They analyzed heart structure of the SMA mice compared with normal mice, and found that there were significant structural changes occurring in the heart of the SMA mice, along with severely impaired left-ventricular function. SMA mice also had significantly lower heart rates. After examining the underlying structure of the mouse heart cells they found it similar to the cellular structure of a heart biopsy from patient with type 3 SMA.

To read the rest of the article from Nationwide Children’s Hospital, click here.

To read the abstract of the journal article, click here.

To learn more about gene therapy, click here.

To learn more about spinal muscular atrophy, click here.