Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes

Mol Ther. 2017 Apr 5;25(4):870-879. doi: 10.1016/j.ymthe.2017.02.015. Epub 2017 Mar 6.


Sporadic inclusion body myositis, a variant of inflammatory myopathy, has features distinct from polymyositis/dermatomyositis. The disease affects men more than women, most commonly after age 50. Clinical features include weakness of the quadriceps, finger flexors, ankle dorsiflexors, and dysphagia. The distribution of weakness is similar to Becker muscular dystrophy, where we previously reported improvement following intramuscular injection of an isoform of follistatin (FS344) by AAV1. For this clinical trial, rAAV1.CMV.huFS344, 6 × 1011 vg/kg, was delivered to the quadriceps muscles of both legs of six sporadic inclusion body myositis subjects. The primary outcome for this trial was distance traveled for the 6-min walk test. The protocol included an exercise regimen for each participant. Performance, annualized to a median 1-year change, improved +56.0 m/year for treated subjects compared to a decline of -25.8 m/year (p = 0.01) in untreated subjects (n = 8), matched for age, gender, and baseline measures. Four of the six treated subjects showed increases ranging from 58-153 m, whereas two were minimally improved (5-23 m). Treatment effects included decreased fibrosis and improved regeneration. These findings show promise for follistatin gene therapy for mild to moderately affected, ambulatory sporadic inclusion body myositis patients. More advanced disease with discernible muscle loss poses challenges.

Keywords: 6-min walk distance; 6-min walk test; Follistatin; adeno-associated virus; gene therapy; sporadic inclusion body myositis.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Aged
  • Animals
  • Biomarkers
  • Biopsy
  • Dependovirus / genetics
  • Dependovirus / immunology
  • Follistatin / genetics*
  • Follow-Up Studies
  • Gene Dosage
  • Genetic Therapy* / methods
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / adverse effects
  • Genetic Vectors / genetics
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myositis, Inclusion Body / diagnosis
  • Myositis, Inclusion Body / genetics*
  • Myositis, Inclusion Body / therapy*
  • Recovery of Function
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome
  • Walk Test


  • Biomarkers
  • Follistatin
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases