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Mechanisms of in vitro synaptic transmission of mis-folded human SOD1

Project Overview

The process by which ALS spreads throughout the body remains a mystery, but Dr. Neil Cashman has spent decades looking at how abnormal changes in shape (scientifically called misfolding) of crucial proteins (the substances that do life processes) in our cells might propagate disease from one cell to another. In particular, for ALS, a protein called superoxide dismutase 1 (SOD1) has been hypothesized as the culprit that misfolds and propagates disease by triggering a domino effect of further SOD1 misfolding. Signals from our brain to our muscles and throughout our nervous system occur through internal wiring of cells called neurons that are interconnected. Between neurons, there is a tiny gap at their connection point called the synapse and to date, there has been no demonstration of misfolded SOD1 being able to cross the synapse to spread toxicity from cell to cell. Using unique aspects of fruit fly (Drosophila) neurons involved in smell, Dr. Cashman has teamed up with a Drosophila expert, Dr. Catherine Cowan, also at UBC, to visualize if this neuronal transmission indeed occurs. If so, Dr. Cashman intends to further examine the characteristics of how SOD1 can cross synapses and even determine if he can develop a test in flies that would allow for screening of drugs that may be able to alter this transmission and possibly be a blocker of ALS spread throughout the body. Ultimately, if the hypothesis is true, the implications would be huge for ALS treatment. Proof that SOD1 misfolding is common to most cases of ALS, and not just the 2% that have hereditary SOD1 mutations, will massively increase the potential value of SOD1 targeted therapeutics that are already in the clinical trial pipeline.

Principal Investigator

Neil Cashman , University of British Columbia

Partners and Donors

ALS Society of Canada

Project Ongoing

Mechanisms of in vitro synaptic transmission of mis-folded human SOD1

  • Program Type

    Team grants

  • Area of research

    Neurodegeneration

  • Disease Area

    ALS

  • Competition

    ALS Canada - Brain Canada Discovery Grants

  • Province

    British Columbia

  • Start Date

    2017

  • Total Grant Amount

    $100,000

  • Health Canada Contribution

    $50,000

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