Antisense oligonucleotide therapy for neurodegenerative disease

• DOI: 10.1172/jci25424
• Publication Date: 2006-07-28T23:39:52Z
• Authors: R. A. Smith
• Keywords: Antisense therapy; Pathogenesis

Neurotoxicity from accumulation of misfolded/mutant proteins is thought to drive pathogenesis in neurodegenerative diseases. Since decreasing levels responsible for such accumulations likely ameliorate disease, a therapeutic strategy has been developed downregulate almost any gene the CNS. Modified antisense oligonucleotides, continuously infused intraventricularly, have demonstrated distribute widely throughout CNS rodents and primates, including regions affected major Using this route administration, we found that oligonucleotides superoxide dismutase 1 (SOD1), one most abundant brain proteins, reduced both SOD1 protein mRNA spinal cord. Treatment initiated near onset significantly slowed disease progression model amyotrophic lateral sclerosis (ALS) caused by mutation SOD1. This suggests direct delivery could be an effective, dosage-regulatable means treating diseases, ALS, where appropriate target are known.