NYSCF Innovator Discovers Mechanism Leading to Toxic Buildup in ALS and Frontotemporal Dementia

New research from the lab of NYSCF — Robertson Investigator Justin Ichida, PhD, at the University of Southern California suggests that a faulty gene can cause toxic buildup and motor nerve cell death in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Mutations in this gene, called C9ORF72, are known to contribute to the onset of these two diseases, causing 10% of all ALS cases as well as an additional 10% of all FTD cases. But why the mutation leads to cell death was previously unknown.

In the study, researchers extracted blood from ALS patients as well as healthy patients and reprogrammed the blood cells to become the motor nerve cells affected by the disease. In the ALS patients, the team observed a mutation in C9ORF72 and cell death. In healthy patients, the researchers found that deletion of C9ORF72 also caused cell death. Both sets of cells could be saved, however, by adding the protein that C9ORF72 usually makes back in.

Further experiments showed that proteins made from C9ORF72 are used to build lysosomes (cellular structures that help break down waste). When C9ORF72 doesn’t work, lysosomes don’t form correctly and waste builds up, eventually killing the cell.

Based on these results, Dr. Ichida’s lab will now begin investigating whether drugs that regulate lysosome function can help alleviate symptoms of ALS and FTD.

For more information, check out the press release from USC or the paper in Nature Medicine.