Muscle plasticity in growing children with cerebral palsy: from myogenesis to treatment

Cerebral palsy (CP) is the most common life-disabling pathology in children. It is caused by a brain lesion, resulting in impaired muscle function. Since muscles are highly plastic tissues, altered muscle growth is a major problem. Yet, its treatment is hindered by insufficient understanding of its pathogenesis. This is the first project to comprehensively describe the time course of macro- and microscopic changes in lower limb muscles of growing children with CP, compared to age-matched peers, using 3D ultrasonography and muscle biopsy, respectively. We will delineate the network of key regulatory factors determining impaired muscle growth and envision pathways to optimize its treatment. So far, hampered muscle growth has mainly been associated with abnormal muscle use, thus classifying it as a secondary process. However, children with perinatal brain lesions may also have impaired myogenesis due to early abnormal neuronal input to the muscle. To explore this pathogenesis, we will evaluate muscles early after the occurrence of the brain lesion, and in separate groups categorized by the age at which the brain lesion occurred. We hypothesize that the etiology of altered muscle growth is a combined process of impaired myogenesis and responses to altered muscle use and treatment. This translational project, covering the time-course analysis of disturbed muscle plasticity, will help characterize different disease presentations, paving the way for novel preventative therapies.