Targeting pathways of disease in Spinal Bulbar and Muscular Atrophy (SBMA)
Summary: Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy’s disease (KD), is adult-onset slowly progressing rare inherited neuromuscular disorder that primarily affects males. As yet there are no effective treatments that can cure the disease or delay its progression. The disease is primarily characterised by muscle weakness and wasting, and degeneration of motor neuron cells within the spinal cord and brain.
Our aim is to establish why motor neurons and muscles degenerate in SBMA by investigating the genes and pathways that underlie disease. The identification of changes that occur early in disease may identify the mechanisms responsible for disease and help establish novel therapeutic targets. This proposal offers the unique opportunity to undertake a comparative study of two platforms that model SBMA, each with its own merits: i) a well-characterised mouse model in which muscle and motor neurons can be examined at various stages of disease, and ii) human cell models, including stem-cell derived motor neurons and patient muscle cells acquired from biopsies. By comparing and contrasting the changes in gene expression in these models of the specific cells affected in SBMA we hope to identify the key changes in gene expression that take place early in disease, identifying a common signature in the pathways of pathology. The results of this study will not only help define novel therapeutic targets with a greater level of confidence by analyzing several complimentary models of SBMA, but also allow us to test treatment strategies in a human cell model of the disease.
