An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study
Timothy M Miller, Alan Pestronk, William David, Jeff rey Rothstein, Ericka Simpson, Stanley H Appel, Patricia L Andres, Katy Mahoney, Peggy Allred, Katie Alexander, Lyle W Ostrow, David Schoenfeld, Eric A Macklin, Daniel A Norris, Georgios Manousakis, Matthew Crisp, Richard Smith, C Frank Bennett, Kathie M Bishop, Merit E Cudkowicz Read More
Background Mutations in SOD1 cause 13% of familial amyotrophic lateral sclerosis. In the SOD1 Gly93Ala rat modelof amyotrophic lateral sclerosis, the antisense oligonucleotide ISIS 333611 delivered to CSF decreased SOD1 mRNAand protein concentrations in spinal cord tissue and prolonged survival. We aimed to assess the safety, tolerability,and pharmacokinetics of ISIS 333611 after intrathecal administration in patients with SOD1-related familialamyotrophic lateral sclerosis.