Funded Grants

Back to results

Investigating the templated propagation and impact of pathogenic FUS in hiPSCs-derived cerebral organoids

Project Overview

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects the human motor system, leading to muscle weakness and ultimately paralysis. In addition to the selective loss of nerve cells controlling muscle movements, buildup of protein aggregates can also be seen in affected nerve cells of ALS patients. Mounting evidence suggests that the buildup of protein aggregates plays a crucial role in the development of ALS. One key protein involved in ALS is Fused in Sarcoma (FUS), which is important for RNA metabolism, including the translation of RNA into proteins. Mutations in FUS cause the protein to change its shape, favoring the formation of aggregates. These FUS aggregates have been found in some ALS patients, both sporadic and familial. Studies suggest that the protein aggregates could spread from cell to cell, contributing to the progression of ALS. However, we still do not know if FUS protein could spread in living human nerve tissues. Recently, the development of induced pluripotent stem cells (iPSCs) technology has made it possible to generate models of the human central nervous system, known as “mini brain”, that are more anatomically and physiologically relevant than commonly used adherent cell models. In this study, we will test if spinal cord samples from FUS-ALS patients can induce the spread of FUS protein aggregates in these mini brain models. We also aim to understand the role of tiny cell particles called extracellular vesicles and cellular connections called tunneling nanotubes in this spread. Addi-tionally, we will investigate if these propagated FUS aggregates affect the cell’s ability to translate RNA into proteins. Our research aims to provide a better understanding of the spread of FUS aggregates, which might be beneficial to a large proportion of ALS patients in the future.

Principal Investigator

Guy Rouleau , Montreal Neurological Hospital and Institute

Partners and Donors

ALS Canada

Project Ongoing

Investigating the templated propagation and impact of pathogenic FUS in hiPSCs-derived cerebral organoids

  • Area of research

    Neurodegeneration

  • Disease Area

    ALS

  • Competition

    ALS Canada - Brain Canada Discovery Grants

  • Province

    Québec

  • Start Date

    2025

  • Total Grant Amount

    $125,000

  • Health Canada Contribution

    $62,500