Blood Test Developed for Lou Gehrig’s Disease

Development is under way of a blood test that may help doctors rule in or rule out a diagnosis of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.

The test will detect and measure misfolded superoxide dismutase 1 (SOD1) protein, which may play a role in both the familial and sporadic forms of this fatal disease.

The test, being developed by Amorfix Life Sciences (Mississauga, ON, Canada) relies on the use of antibodies from the immune system, which act as "molecular magnets" to detect and measure improperly folded SOD1 protein. At the present time, clinicians must rely on a combination of clinical findings and imaging to confirm the diagnosis of ALS, as there is no diagnostic test or biomarker at their disposal.

About 20% of familial ALS cases are associated with mutations in the gene encoding SOD1, a classically cytosolic free radical defense enzyme. Evidence is accumulating that all types of ALS, familial and sporadic, are associated with SOD1 misfolding, oxidation, and aggregation. Neural deposits of aggregated misfolded SOD1 have been detected in familial ALS, and also in sporadic ALS, and biochemical evidence of SOD1 misfolding has also been detected in sporadic ALS. Positive feedback loops have been identified between protein misfolding and excitotoxicity, suggesting that these two pathogenic processes are not mutually exclusive in ALS.

Neil Cashman, MD, Amorfix chief scientific officer, with colleagues at the University of British Columbia (Vancouver, BC, Canada) has shown that even normal SOD1 protein has a propensity to misfold, after which it induces misfolding in neighboring SOD1 protein molecules. The propagation of misfolded SOD1 protein in the body appears to drive cell-to-cell and region-to-region spread of ALS in both the familial and sporadic forms of the disease. Amorfix plans to capitalize on this discovery and existing scientific expertise to develop a simple blood test using magnetic and fluorescent beads coupled to antibodies that would measure misfolded SOD1 in blood.

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Amorfix Life Sciences
University of British Columbia