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Detection of misfolded TDP-43 in CSF of ALS cases: Diagnostic potential of confirmation-specific antibodies

Principal Investigator:
  • Yulong Sun, University Health Network (University of Toronto)
  • ALS Society of Canada

Project Overview

A more streamlined way to diagnose ALS earlier is desperately needed as current methods can take up to two years and rely heavily on ruling out other conditions that share similar symptoms. One of the hallmarks of ALS for 97 per cent of cases is the accumulation of misfolded TDP-43 protein in motor neurons. One theory about how the disease spreads from cell-to-cell is that misfolded TDP-43 is expelled from motor neurons in ALS and picked up by other cells. Some of this expelled TDP-43 may end up in cerebral spinal fluid (CSF).

Dr. Sun has developed two antibodies which bind exclusively to misfolded TDP-43 with the aim of making them more detectable in body fluids, something current lab tests cannot accomplish. He and his colleagues have previously shown pilot data that these antibodies are capable of detecting misfolded TDP-43 in post-mortem patient brain tissue.

In this project, he seeks to develop a new lab test that can detect misfolded TDP-43 in CSF. First, using advanced imaging technologies, he will test the two antibodies to see if they can detect misfolded TDP-43 in 40 samples of CSF already collected from people living with ALS at the Sunnybrook ALS Clinic. If successful, he will then develop a simple lab test that may help doctors diagnose ALS earlier and monitor disease progression.