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Pathogenic Mechanism of C9orf72 haploinsufficiency in ALS/FTLD: a road to therapeutic discovery

Principal Investigator:
  • Janice Robertson, University of Toronto
  • ALS Society of Canada

Project Overview

In 2011, scientists discovered that hereditary mutation of a previously unstudied gene called C9ORF72 was the most prominent cause of both ALS and frontotemporal dementia (FTD). These mutations were found in both hereditary (familial) and non-hereditary (sporadic) forms of the disease and comprise about one third of all cases. Since that discovery, ALS researchers have aimed to understand the normal function of C9ORF72, determine how mutations in the gene can cause the disease and create animal and cellular models to study it. Previously, Dr. Janice Robertson published a landmark paper that demonstrated the existence of two different forms of C9ORF72 protein, including one that localized to the outer layer of the cell’s command centre called the nucleus. This was the first indication of what would become a breakthrough discovery by three teams independently showing that mutations in C9ORF72 disrupt the movements of critical substances into and out of the nucleus. In this Hudson project, the team led by Dr. Robertson will pursue a comprehensive understanding of the normal functions of C9ORF72 and provide a better determination of whether loss of these functions via mutation may cause or contribute to ALS.