Propagated protein misfolding of SOD1 in ALS: Exemplar for neurodegeneration

Principal Investigator: 
University: 
University of British Columbia
Faculty: 
Medicine
Department: 
Division of Neurology and Djavad Mowafaghian Centre for Brain Health
Award Type: 

MSFHR supported Dr. Neil Cashman’s award as one of two interprovincial teams from across Canada funded through Brain Canada’s Multi-Investigator Research Initiative (MIRI) in 2013. The MIRI supports the research of multidisciplinary teams and aims to accelerate novel and transformative research that will fundamentally change the understanding of nervous system function and dysfunction and its impact on health. MSFHR committed funding over three years to support the work of Cashman’s BC-based research activities and research led by fellow MIRI recipient Dr. Terrance Snutch on the role of brain calcium channels in brain disorders. Additional support was provided by Genome BC, the University of British Columbia (UBC)/Vancouver Coastal Health and two Quebec-based research institutes.

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, is a progressive fatal disease that affects the nerve cells responsible for muscle movement (motor neurons). ALS is characterized by the systematic paralysis of muscles due to the progressive death of motor neurons. An estimated 2,500 to 3,000 Canadians suffer from the disease, for which there is no cure or effective treatment. Each day, two to three people are lost to ALS, with 80 percent of affected individuals dying within two to five years of diagnosis. 

A study led by clinical neurologist and neuroscientist Dr. Neil Cashman at UBC has revealed how factors that cause ALS can be transmitted from cell to cell throughout the nervous system and suggests the spread of the disease could be blocked, pointing to new therapeutic approaches.

Neurodegenerative diseases like ALS belong to a larger group of illnesses known as protein misfolding diseases. Cashman, who holds the UBC Canada Research Chair in Neurodegeneration and Protein Misfolding, built on his hypothesis that certain proteins implicated in ALS, when abnormally shaped or misfolded, are prone to accumulate and cause motor neuron death. This disease mechanism has also been found in other neurological diseases, such as Alzheimer’s and Parkinson diseases. 

Cashman’s team used therapeutic antibodies that target and block these misfolded proteins to better understand the protein misfolding process and how the disease is transmitted throughout the nervous system. Cashman’s work can lead to identifying the best ways to stop the progressive neurological damage seen in ALS through the development of targeted treatments.

Host Institution: 
University of British Columbia
Research Location: 
University of British Columbia
Djavad Mowafaghian Centre for Brain Health
Year: 
2013