Cerebral Palsy (CP) is a neurologically non-progressive condition caused by a perinatal insult to the brain. While the brain lesion is non-progressive, children with CP have progressive changes to their skeletal muscles including development of spasticity, muscle atrophy, shorter muscles, and development of debilitating muscle contractures, which may manifest as a reduced range of joint excursion. Satellite cells are muscle stem cells that reside between the basal lamina (a layer of extracellular matrix) and the sarcolemma (the plasma membrane) of muscle fibers. In typically developing (TD) children, when muscles grow or injury occurs, satellite cells are mobilized, they proliferate, differentiate into mononucleated myoblasts, and then fuse together to form polynucleated myotubes. Myotubes ultimately become new contracting muscle fibers or replace damaged tissue.
We previously reported a 60-70% depletion of resident satellite cell number in contractured muscle tissue from children with CP. In soon-to-be-published data, we also show that myoblasts derived from satellite cells isolated from contractured muscles in CP have a decreased capacity to fuse and to produce myotubes in vitro. This impairment is associated with epigenetic changes affecting DNA methylation of genes involved in myogenesis. This suggests that muscle contractures in CP are associated with loss of satellite cells number and myogenic potential, which may be dependent on epigenetic changes affecting the physiology (proliferation and differentiation) of these cells. These mechanisms may play an adverse role in postnatal muscle growth and repair in children with CP leading to the development of muscle contractures and other pathologic changes in their musculoskeletal system. A pharmacological treatment of children with CP with new drug therapies affecting DNA methylation may prevent or cure the progression of muscle contractures. Such treatment, in combination with physical therapy may permit CP satellite cells to maintain muscle growth and repair during development, thus improving strength and range of motion in these patients. This research is meant to assist with the development of specific and personalized treatment planning for the 750,000 individuals and the 11,000 children born with CP each year in the USA (2008 census).