Researchers at the University of Toronto, in a new study, have reportedly developed novel antibodies for tracking a gene involved in amyotrophic lateral sclerosis (ALS), otherwise known as Lou Gehrig’s disease.

Published July 14 online in the journal Annals of Neurology, the study suggests that these antibodies for tracking C9orf72—the gene involved in ALS—uncovers a link between the genetic cause of ALS and its pathology, according to a news release from the University of Toronto.

The release explains that Professor Janice Robertson and her team at the Tanz Centre for Research in Neurodegenerative Diseases developed novel antibodies that not only specifically detected C9orf72 in human tissues, but could also distinguish between both the long and short isoforms.

“Using these antibodies, we have made the remarkable discovery that C9orf72 is localized to the nuclear membrane in healthy neurons, but is mislocalized to the plasma (outer membrane) in diseased neurons,” Robertson says in the release.

Robertson and her team also showed that C9orf72 directly interacts with components of the nuclear shuttling complex, which is responsible for the movement of proteins across the nuclear membrane. One such protein is TDP-43, which normally resides in the nucleus but is wrongly localized to the cytoplasm in diseased neurons in ALS. TDP-43 accumulation and aggregation in the cytoplasm diagnoses most ALS cases—but the link with C9orf72 was absent, per the release.

Now through the use of the C9orf72 antibodies, the Robertson lab has found that loss of C9orf72 from the nuclear membrane correlates with TDP-43 pathology. These results suggest that defects in C9orf72 affect the proper functioning of the nuclear shuttling complex, resulting in TDP-43 buildup in the cytoplasm, the release explains.

“The possible involvement of C9orf72 in the shuttling between nucleus and cytoplasm opens intriguing new avenues of research into the causes of ALS—and hopefully, one day an effective treatment or cure,” says Robertson, a Canada Research Chair in ALS, in the release.

[Source(s): University of Toronto, Science Daily]