Expanded Access to the FUS-ASO, Jacifusen for the Treatment of Mutant FUS-Associated ALS.

The specific aims of this proposal is to test the safety and efficacy of an anti-sense oligonucleotide (ASO) targeting transcripts of the gene FUsed in Sarcoma (FUS) as an investigational treatment in patients with ALS caused by mutant FUS. The ASO, called jacifusen, is designed to lower the levels of FUS transcript and protein in the brain and spinal cord and thereby to decrease the toxic effects of mutant FUS. The objective of this project is to determine whether chronic administration of jacifusen can reduce or stabilize neurological decline using clinical endpoints. This proposal also aims to identify biomarkers of FUS-ALS for the purpose of diagnosis and as a measure of target engagement and efficacy of jacifusen and other FUS-ALS candidate therapeutics.