Project Overview

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disease with distinct genetic contributions. However, even for genetically defined components of ALS, there remains great variability in disease onset and progression. It is generally thought that a contribution of genetics, environmental factors, and time all contribute the natural history of neurodegenerative diseases like ALS. Microbiome-host interactions could also affect disease onset and progression, and identifying neuroprotective bacterial strains could form the basis for new therapies. We discovered a bacterial strain (HA-114) that protects motor neurons from degeneration in several ALS animal models that and our investigations implicate mitochondrial β-oxidation as a key mechanism for neuroprotection. Mitochondrial β-oxidation is the catabolic process by which fatty acid molecules are broken down in the mitochondria, generating acetyl-CoA to participate in energy production.
We hypothesize that in ALS, motor neurons are in an energy deficit undermining the efficacy of cellular stress response mechanisms ultimately leading to neuronal dysfunction and cell death. Metabolic dysfunction has been observed in ALS patients and many research models. In particular, ALS is associated with hypermetabolism and elevated basal energy expenditure, which is accompanied by increased oxidation of fatty acids which may occur in advance of motor neuron degeneration. We speculate that HA-114 bolsters mitochondrial β-oxidation, perhaps by providing key metabolites, leading to a restoration of lipid and energy homeostasis leading to neuroprotection.

Specific Aims
(1) Investigate the mechanism of HA-114 mediated neuroprotection in a mammalian ALS model, with a special focus on metabolism and lipid homeostasis.
(2) Metabolic profiling of HA-114 to identify the neuroprotective molecules for therapeutic development.

We have discovered a bacterial strain that suppresses neurodegeneration linked to ALS. Learning more about the genetic, molecular and biochemical mechanisms of this strain may have clinical applications for ALS.

Principal Investigator

Alex Parker , Centre hospitalier de l’Université de Montréal

Team Members

Matthew Ruiz, Montreal Heart Institute, Université de Montréal

Partners and Donors

ALS Canada