Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy, affecting about 1 in 3000 males each year. It is an X-linked recessive disease, in which mutations in the dystrophin gene causes progressive and degenerative muscle weakness. DMD is generally lethal by age 30.
Dr. Spiegelman and colleagues found that a protein called PGC-1alpha regulates the point of connection between the end of a motor neuron and a muscle fiber - what researchers call the "neuromuscular junction." Electrical impulses travel through the neuromuscular junction, ultimately causing the muscle to contract. Previous research has shown that PGC-1alpha expression is induced by physical exercise and motor neuron activity, and mediates the anti-atrophic effects of nerve activity on muscle mass.
Dr. Spiegelman and colleagues analyzed the function of PGC-1alpha in a mouse model of DMD. They found that PGC-1alpha activates the expression of several genes that are aberrantly inactivated in DMD. In fact, by inducing PGC-1alpha expression in these transgenic mice, the scientists were able to improve DMD symptoms.
"These data clearly show that experimental elevation of PGC-1 alpha has therapeutic promise in an animal model of Duchene's muscular dystrophy. We hope this will lead eventually to therapeutics for a terrible disease for which there is no effective treatment at the present time," explains Dr. Spiegelman.
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"We are bringing together the best of the developmental biology world with the best of the stem cell world and starting the conversation, with the focus on how to get regeneration to work in a mammal," said Edward Scott, Ph.D., a professor of molecular genetics and director of the Program in Stem Cell Biology at the College of Medicine. "Essentially, our body can heal itself, and that's why many of us live to be 80. But we can't do things like grow an arm or finger as we did in the early stages of our development. We want to learn how to turn those systems back on in people."
Recently, studies have shown humans possess some of the same genes and communication pathways used by some of nature's most remarkably regenerative animals.
Already, UF McKnight Brain Institute scientists have discovered more than 100 genes associated with all major human neurological diseases in a simple marine snail, as well as more than 600 genes that control development. In the realm of adult human stem cells, Brain Institute researchers have shown ordinary human brain cells can generate new brain tissue in mice and produce large amounts of new brain cells in culture for use as possible replacements for dead or injured cells.
The UF project is "bold" because it takes a comprehensive view of regenerative medicine, according to Arlene Y. Chiu, Ph.D., director for scientific activities at the California Institute for Regenerative Medicine.
"We are all excited by the great potential of stem cells to repair damage and return function," Chiu said. "It remains a great mystery, however, why some organisms are able to renew tissues, organs and even restore whole limbs while other related animals are not. Even within a single organism, we find that some tissues have a far more robust ability to replenish and replace cells than others. Yet we do not understand the bases for these differences."
The Regeneration Project will shortly begin establishing its think tank of international scientists, Steindler said.
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