SOD1 Suppression with Adeno-Associated Virus and MicroRNA in Familial ALS

N Engl J Med. 2020 Jul 9;383(2):151-158. doi: 10.1056/NEJMoa2005056.


Two patients with familial amyotrophic lateral sclerosis (ALS) and mutations in the gene encoding superoxide dismutase 1 (SOD1) were treated with a single intrathecal infusion of adeno-associated virus encoding a microRNA targeting SOD1. In Patient 1, SOD1 levels in spinal cord tissue as analyzed on autopsy were lower than corresponding levels in untreated patients with SOD1-mediated ALS and in healthy controls. Levels of SOD1 in cerebrospinal fluid were transiently and only slightly lower in Patient 1 but were not affected in Patient 2. In Patient 1, meningoradiculitis developed after the infusion; Patient 2 was pretreated with immunosuppressive drugs and did not have this complication. Patient 1 had transient improvement in the strength of his right leg, a measure that had been relatively stable throughout his disease course, but there was no change in his vital capacity. Patient 2 had stable scores on a composite measure of ALS function and a stable vital capacity during a 12-month period. This study showed that intrathecal microRNA can be used as a potential treatment for SOD1-mediated ALS.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / therapy*
  • Dependovirus
  • Fatal Outcome
  • Gene Silencing
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Injections, Spinal
  • Male
  • Meningoencephalitis
  • MicroRNAs / therapeutic use*
  • Middle Aged
  • Mutation
  • Proof of Concept Study
  • Spinal Cord / chemistry
  • Spinal Cord / pathology
  • Superoxide Dismutase-1 / analysis
  • Superoxide Dismutase-1 / cerebrospinal fluid*
  • Superoxide Dismutase-1 / genetics
  • Vital Capacity
  • Young Adult


  • MicroRNAs
  • SOD1 protein, human
  • Superoxide Dismutase-1

Supplementary concepts

  • Amyotrophic lateral sclerosis 1