CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS

Neurology. 2014 Nov 11;83(20):1780-8. doi: 10.1212/WNL.0000000000000926. Epub 2014 Sep 19.


Objective: This study evaluated the efficacy and safety of ATL1102, an antisense oligonucleotide that selectively targets the RNA for human CD49d, the α subunit of very late antigen 4, in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: In a multicenter, double-blind, placebo-controlled randomized phase II trial, 77 patients with RRMS were treated with 200 mg of ATL1102 subcutaneously injected 3 times in the first week and twice weekly for 7 weeks or placebo and monitored for a further 8 weeks. MRI scans were taken at baseline and weeks 4, 8, 12, and 16. The primary endpoint was the cumulative number of new active lesions (either new gadolinium-enhancing T1 lesions or nonenhancing new or enlarging T2 lesions) at weeks 4, 8, and 12.

Results: A total of 72 patients completed the study and 74 intention-to-treat patients were assessed. ATL1102 significantly reduced the cumulative number of new active lesions by 54.4% compared to placebo (mean 3.0 [SD 6.12] vs 6.2 [9.89], p = 0.01). The cumulative number of new gadolinium-enhancing T1 lesions was reduced by 67.9% compared to placebo (p = 0.002). Treatment-emergent adverse events included mild to moderate injection site erythema and decrease in platelet counts that returned to within the normal range after dosing.

Conclusions: In patients with RRMS, ATL1102 significantly reduced disease activity after 8 weeks of treatment and was generally well-tolerated. This trial provides evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders.

Classification: This study provides Class I evidence that for patients with RRMS, the antisense oligonucleotide ATL1102 reduces the number of new active head MRI lesions.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Disability Evaluation
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Integrin alpha4 / chemistry*
  • Integrin alpha4 / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Oligodeoxyribonucleotides, Antisense / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Oligodeoxyribonucleotides, Antisense
  • Integrin alpha4