Researchers led by Prof Giampietro Schiavo, UK DRI at UCL, have used two new mouse models of motor neurone disease (MND) to show that early disease mechanisms may differ depending on the causative gene. Deficits in transport along nerve cells preceded symptoms in one but not the other model, suggesting that therapeutics may have to be tailored to individuals according to their genes.
MND, also known as amyotrophic lateral sclerosis (ALS), is a rare but fatal, progressive neurodegenerative disease resulting in loss of motor neurons, muscle wasting, and ultimately death - most often due to respiratory failure. The disease is thought to develop from a complex interplay between genetic and environmental factors. Mutations in several key genes are known to cause MND that result in faulty versions of proteins essential for life.
A number of disease mechanisms have been investigated in the search for effective treatments, and disruption to the transport network in neurons is an emerging central theme. In this study, published today in Cell Reports, Prof Schiavo, Dr James Sleigh and their teams set out to explore this phenomenon in two new transgenic mouse models of MND caused by faulty TDP-43 or FUS proteins. TDP-43 and FUS have several similarities and common functions in healthy brain, suggesting that they may share disease mechanisms.