Isis Pharmaceuticals Inc. has teamed up with a trio of academic groups to develop antisense therapeutics for the largest subset of patients with amyotrophic lateral sclerosis,1-3 and all three teams have converged on a common mechanism of neurotoxicity caused by carrying hexanucleotide repeat expansions in the C9orf72 gene. Antisense oligonucleotides targeting the repeats decreased the toxicity in vitro. The teams now need to determine whether the reduced toxicity correlates with decreased neurodegeneration in patients.
Amyotrophic lateral sclerosis (ALS) is a neurological disorder that involves muscle wasting, stiffness and spasticity due to loss of motor neurons. ALS often overlaps with frontotemporal lobar dementia (FTLD), a disease that involves neuronal degeneration in the frontal and temporal cortices.
Both diseases can occur as inherited familial disorders or sporadically with no known familial link.
The GGGGCC repeat expansion in the first intron of C9orf72 (chromosome 9 open reading frame 72) is the