Publications

Antisense oligonucleotides are synthetically manufactured short segments of deoxynucleotide sequences that cause targeted gene transcription inhibition. They are designed to interact with their specific complementary mRNA, thereby interfering with transcript stability and/or translation.1,2 This process activates endogenous RNAse-H, which destroys the target mRNA and releases the antisense molecule to act on another mRNA transcript. EN101 antisense (Monarsen) acts against both the catalytic and noncatalytic contributions of acetylcholinesterase (AChE). It was designed to induce destruction of the read-through splicing variant of AChE3 and has shown promising short- and long-term therapeutic effects in experimental myasthenia gravis (MG), both IV and orally.4The objectives of this open label human study with oral EN101 were 1) to evaluate the safety of short-term administration in seropositive MG and 2) to assess possible efficacy by monitoring changes in patients’ functional status.