Motor Neuron Disease (MND) is a fatal neurodegenerative disease for which there is no cure. For most patients, death occurs within 2–5 years of diagnosis. While the primary pathology in MND is the death of motor neurons, there is evidence that defective energy metabolism affects disease pathogenesis. Moreover, increased body mass index and high calorie supplementation is associated with improved prognosis in MND patients. Thus, we hypothesise that in MND, the state of metabolic flux modifies disease course, and modulation of metabolic homeostasis will aid in sustaining survival. We have studied mouse models and human subjects to investigate how altered metabolic homeostasis impacts disease outcome.
During this talk, I will present data that demonstrates key endocrine and physiological adaptations that facilitate the mobilisation and uptake of energy substrates to meet increased metabolic demand. Maintenance of optimal energy supply plays an integral role in slowing disease progression and sustaining survival in MND. Our studies not only establish the disease-promoting role of altered energy metabolism in MND, but also pave the way for future clinical testing of novel therapeutics aimed at improving metabolic capacity to prevent the death of neurons and muscle in neurodegenerative diseases.