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Canadian Researchers Discover New ALS Gene Mutation

In what he describes as, "a purely Canadian discovery", Dr. Michael Strong`s laboratory at Western University have discovered a new gene that causes ALS.  Last year, a project led by postdoctoral fellow Dr. Cristian Droppelmann described a protein called rho guanine nucleotide exchange factor (RGNEF) which was identified in clumps (called aggregates or inclusions) that appear inside of sick motor neurons and have long been associated with the disease pathology. Further investigation revealed a mutation in the gene that makes RGNEF (called ARHGEF28) as a previously unknown cause of hereditary ALS.

ALS-causing mutant genes create abnormal proteins that are a scientist`s best tool for understanding the disease process and identifying potential new treatment targets. By examining what happens in a living cell or animal that is designed to make the abnormal protein, researchers can find what processes are affected and look at ways to correct the problem.

The first ALS gene to be discovered was in 1993 (SOD1) and it was the only tool available until another gene was discovered in 2006 (TARDBP – makes TDP-43). Since then, additional ALS genes have been discovered including FUS and C9ORF72, which provide many new avenues for studying how motor neurons get sick and lose their function of helping muscles move. These more recent genes share a common link in that they are involved in what is called RNA metabolism. RNA is a transportable form of genetic information that is critical to the creation of proteins, which perform all of our living functions. RGNEF is important in the regulation of RNA for a particular protein that is involved in neuronal structure (called neurofilament light or NF-L) and is well established to play a role in ALS.

Most of these new genes have been discovered through increasingly sophisticated techniques in reading the DNA of affected individuals. However, Dr. Strong s study "builds on the old fashioned way of discovering things – look for protein, find it pathological in ALS, and then see if it is mutated." Further studies will reveal how prominent this mutation is in the 10% of cases that comprise familial ALS. Ultimately, this discovery may prove to be a crucial link in our understanding of ALS and is yet another good demonstration of how Canada is a world leader in ALS research.

* Watch Dr. Strong's 'Understanding Research' video here to see the achievements of his lab and how your support dollars work for ALS research *