The new therapy enhanced muscle strength, improved gross motor skills and increased the lifespan in a SMA model.

"This therapy does not directly target the disease-causing gene; instead it targets the pathways that affect muscle maintenance and growth," said Chris Lorson, investigator in the Christopher S. Bond Life Sciences Center and associate professor of veterinary pathobiology in the MU College of Veterinary Medicine. "We administered a particular protein, follistatin, to SMA mouse models to determine if enhanced muscle mass impacts the symptoms of SMA. After treatment, the mice had increased muscle mass, gross motor function improvement and an increase in average life span of 30 percent."

With the therapy, MU researchers inhibited myostatin, a protein that limits muscle tissue growth. Myostatin activity can be reduced significantly by enabling several proteins that bind to myostatin, including follistatin. When myostatin is inhibited, muscle mass and strength increase.

SMA is caused by the loss of survival motor neuron-1(SMN1). Humans have a nearly identical copy gene called SMN2. Because of a single molecular difference, SMN2 alone cannot compensate for the loss of SMN1.

"While most work in the SMA field has logically focused on targeting the SMN2 gene, the results of this study suggest that skeletal muscle is a viable therapeutic target that may reduce the severity of some SMA symptoms," said Lorson, who also is the scientific director for FightSMA, a private spinal muscular atrophy research foundation in Richmond, Va. "Because follistatin does not alter the expression level of SMN protein, the most effective treatment would combine strategies that directly address the genetic defect in SMA as well as SMN-independent strategies that enhance skeletal muscle."

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Another study, also led by Dr. Faraone, is the first genome-wide study of response to methylphenidate in ADHD children. Dr. Faraone and his colleagues, examined genetic markers across the entire human genome to search for genes that may someday be used to predict which children respond most favorably to the stimulant medications used to treat ADHD. It demonstrated that, although there are likely to be genetic factors that are associated with stimulant efficacy in children with ADHD, there are no single genes with a very large impact on treatment response.

"Previous efforts at understanding the role of candidate genes in the response to pharmacotherapy have been inconclusive," says Eric Mick, the study's first author. "There is a great need for larger more rigorous studies of genetic predictors of treatment response."

Research was conducted, in part, through the Genetics Analysis Information Network (GAIN), a public-private partnership between the National Institutes of Health and the private sector with the goal of promoting genome mapping for various complex diseases.

Recent advances in these technologies have facilitated the cost-effective genotyping of hundreds of thousands of DNA markers. Genome-wide association studies (GWAS) hold great promise for identifying genetic variants for disease. GWAS have already been successful in identifying variants associated with many complex diseases including obesity, age-related macular degeneration, Type I and Type II diabetes, Crohn's disease and prostate cancer.

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