TDP-43, SOD1, and FUS proteinopathies in vivo: interrogating prion-like mechanisms and drug rescue in zebrafish and ALS hiPSC-derived neuron xenotransplant models

In ALS research, zebrafish are useful models to study the disease in the lab, as they share key genes with humans, develop quickly, and have a well-characterized nervous and motor system. To enhance this organism even further, Dr. Michele Duval will transplant human induced pluripotent stem cells (hiPSC) from people living with ALS into zebrafish, creating a novel model of the disease.

In this model, she will look closely at three key proteins in ALS that behave abnormally in people with the disease: TDP-43, SOD1, and FUS. These proteins often misfold and clump together in ways that are known to contribute to disease progression. One theory by ALS researchers is that these proteins can potentially spread from cell to cell in a prion-like fashion. Dr. Duval will test whether these misfolded proteins can trigger similar changes in healthy proteins and move between cells. The goal is to also capture valuable information that can be used in drug screening.

Dr. Duval’s research can help us uncover how these misfolded proteins affect the brain and identify new ways to stop progression. By also using this unique model to test potential treatments that target protein misfolding, her research can offer hope for both inherited and non-genetic forms of the disease.

Dr. Duval has combined training and expertise in neurology and neuroscience that allows her to connect discoveries in the lab with the realities of patient care. Her ultimate goal is to be a clinician scientist developing treatments for ALS that not only target the disease’s biological mechanisms, but also reflect the lived experiences and needs of those affected.

Since 2007, Clinical Research Fellowships have been a key part of our commitment to building the next generation of clinician-scientists in Canada. These fellowships strengthen the Canadian ALS Research Network (CALS) by supporting early-career researchers who bridge the gap between laboratory discoveries and clinical care.