Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurological disorder that attacks the nerves and muscles. Currently there is no known cure or effective treatments. The latest findings provide a tool for recognizing misfolded conformations of the enzyme superoxide-dimutase-1 (SOD1). Mutations in the gene encoding SOD1 cause approximately one to two per cent of all ALS cases.

“This antibody will enable researchers to investigate whether misfolded SOD1 is involved in other forms of ALS,” said Professor Janice Robertson from the Centre for Research in Neurodegenerative Diseases, and one of the lead authors of the study. “This is important to determining if SOD1 is relevant in ALS cases that are not caused by mutations in SOD1. If this is the case, then the antibody could potentially be used in biomarker studies to facilitate earlier diagnosis of the disease.”

The antibody, named SOD1-exposed-dimer-interface antibody (SEDI-antibody), also opens up the possibility of developing immunization strategies for the treatment of ALS caused by SOD1 mutations, according to Professor Avi Chakrabartty from the Ontario Cancer Institute, senior author of the study. “The SEDI antibody also has utility in drug discovery efforts for identifying chemical chaperones that prevent or reduce misfolding of SOD1 in ALS ,” said Chakrabartty .

Over 114 mutations have been identified and it is not yet known how so many different mutations result in the same disease, while the normal enzymatic function of SOD1 is not affected.; Source: University of Toronto