$75,000 awarded to Amélie Poulin-Brière, a PhD student co-supervised by Dr. Jean-Pierre Julien and Dr. Silvia Pozzi at Centre de recherche CERVO, Université Laval.
Recent studies from Dr. Julien’s lab suggest that the cerebrospinal fluid (CSF) of sporadic ALS patients (e.g., those without a family history of disease) may contain toxic factors that promote the spread of the disease throughout the central nervous system. Researchers hypothesize that the toxic effects may be due to the presence of misfolded TDP-43 and SOD1 proteins within the CSF, which have the potential to spread toxicity from cell-to-cell through a chain reaction inducing protein misfolding in healthy cells.
Previous studies revealed that when CSF collected from sporadic ALS patients is introduced into the CSF of mice, it can trigger neurodegeneration and functional deficits that are hallmark of ALS. In this project, Amélie will co-infuse CSF from sporadic ALS patients with antibodies that specifically target TDP-43 to investigate if depletion of TDP-43 may have a protective effect and how this might occur. She will then use antibodies to remove all TDP-43 or SOD1 from the CSF samples prior to infusion and examine the effect on disease. If these mice show less disease features compared to those infused with CSF still containing TDP-43 and SOD1, it will further implicate these proteins as potential contributors to the spread of ALS and highlight them as key therapeutic targets.
The results gained from this work hope to provide more insight into the mechanisms that underly the progression of ALS and aim to reveal whether targeting TDP-43 and SOD1 proteins in the CSF represents a viable strategy to explore for the treatment of ALS.