Motor neurone disease (MND) is a devastating neurological disorder that strips people of their capacity to interact with the world. MND locks people in their bodies until they die from respiratory failure or associated complications, usually within 27 months of diagnosis. Clearly, there is an urgent need to develop strategies to treat this disease.
The Bedside to Bench to Bedside approach
To accelerate our capacity to find a cure or treatment for MND, we must develop innovative and integrative approaches that evolve from previous successes. Research strategies that are based on bench to bedside translation have provided significant breakthroughs to treat disease. In MND, however, this has not been the case. Indeed, the only compound that provides limited benefits in MND was first developed at the bedside, tested at the bench, and then brought back to the bedside as a treatment.
In 2014 I initiated a Bedside to Bench to Bedside initiative, forming a multidisciplinary research program that integrates neurologists, clinical researchers, stem cell researchers, neuroscientists, physiologists, and biomedical researchers across multiple research centres. The vision was to develop comprehensive and innovative screening platforms that would facilitate the identification of novel mechanisms that could be targeted to improve the quality of life and to extend the survival of people living with MND. Integral to this vision was the implementation of a patient-directed research agenda. The Bedside to Bench to Bedside approach allows us to focus on the needs of each individual patient, and it will enhance our capacity to develop tailored treatments for MND.
Our studies in patients with MND have allowed us to investigate whether an inability to maintain metabolic homeostasis may impact a patient’s quality of life, while accelerating the rate of disease progression. Our results confirm that the metabolic needs of some MND patients are greatly increased, and that changes in whole-body energy metabolism may worsen their disease symptoms. In translating this knowledge from the bedside to the bench, we have identified defects in the processes that regulate energy metabolism in the brain and muscle of preclinical models of MND. I am now focussed on investigating the pathways that control energy metabolism in neurons and muscle that have been derived from MND patient induced pluripotent stem cells. As part of these studies I will test compounds that target metabolic flux in these neurons and muscle, with the specific goal of improving energy metabolism to sustain their function and survival. Ultimately, the translation of positive research findings in human-derived cells from the bench back to the bedside will expedite clinical trials for MND.