Study Supports Antisense Molecule for MG

Scientists in Israel and the United Kingdom announced in the Aug. 14 issue of Neurology that an experimental compound known as EN101 (also called Monarsen) appears to be safe and possibly effective in treating myasthenia gravis (MG).

EN101 is a so-called antisense molecule, designed to block the synthesis of the protein known as acetylcholinesterase (AchE). This protein is an enzyme that normally degrades acetylcholine, a carrier of signals from nerve to muscle. In MG, a treatment goal is to increase acetylcholine action at the nerve-muscle junction to compensate for a mistaken attack on this area by the immune system. Interfering with AchE is one way to accomplish this.

Zohar Argov at Hadassah University Hospital in Jerusalem, with colleagues at other Israeli institutions and at Ester Neuroscience in Herzliya, Israel, and Hope Hospital in Salford, UK, gave oral EN101 to 16 people with MG in an open-label trial, meaning trial participants knew they were getting the experimental drug.

There were no serious side effects or adverse events.

Thirteen participants showed improvement in their quantitative MG score, which measures functional status, although few had clear clinical improvement, such as disappearance of eyelid weakness.

Fourteen of the participants reported subjective improvement with EN101 compared to their standard medication, pyridostigmine.

In an editorial in the same issue of Neurology, Henry Kaminski at Saint Louis (Mo.) University Medical Center writes that “this trial suggests a therapeutic benefit, which should bolster hope for this approach for drug development” not only for MG but for other diseases in which it’s desirable to block the synthesis of a protein.

He notes, “The present short-term study demonstrates safety in a small group of patients, but also a strong suggestion of efficacy.” He also finds it encouraging that an antisense drug appears to be effective when given by mouth.