Further developments with antisense treatment for myasthenia gravis

Ann N Y Acad Sci. 2012 Dec:1275:13-6. doi: 10.1111/j.1749-6632.2012.06825.x.

Abstract

We present further developments in the study of the antisense oligonucleotide EN101. Ongoing in vitro and in vivo studies demonstrate that EN101 is a TLR9-specific ligand that can suppress pro-inflammatory functions and shift nuclear factor kappa B (NF-κB) from the pro-inflammatory canonical pathway to the anti-inflammatory alternative pathway, which results in decreases acetylcholinesterase (AChE) activity. Preliminary results of a double-blinded phase II cross-over study compared 10, 20, and 40 mg EN101 administered to patients with myasthenia gravis. Patients were randomly assigned to one of three treatment groups in weeks 1, 3, and 5 and received their pretreatment dose of pyridostigmine in weeks 2 and 4. Thus far, all doses show a decrease in QMG scores, with a greater response to higher doses.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Acetylcholinesterase / blood
  • Animals
  • Cross-Over Studies
  • Double-Blind Method
  • Humans
  • Myasthenia Gravis / drug therapy*
  • Oligodeoxyribonucleotides / therapeutic use*
  • Oligonucleotides, Antisense / therapeutic use*
  • Rats

Substances

  • EN101
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • Acetylcholinesterase