New Myasthenia Drug Under Study

A drug known as Monarsen (formerly EN101), developed by Ester Neurosciences in Herzelia, Israel, is being studied in the UK under the direction of Jon Sussman at Hope Hospital in Greater Manchester. If all goes well, testing may be expanded to the United States and Europe.

In myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome and some congenital myasthenic syndromes, patients benefit from drugs that prolong the action of acetylcholine at the junction of nerve and muscle fibers.

In MG, the immune system mistakenly attacks receptors for acetylcholine on muscle cells. In Lambert-Eaton syndrome, the immune system inhibits acetylcholine’s release from nerve fibers. And in some congenital myasthenic syndromes, the action of acetylcholine is insufficient because of a genetic mutation that affects the neuromuscular junction.

A common treatment for myasthenia is pyridostigmine (Mestinon), which interferes with the breakdown of acetylcholine by the enzyme AchE. But pyridostigmine’s actions are limited and, at high doses, it can have unwanted side effects.

Monarsen targets AchE before it’s synthesized, while pyridostigmine targets the finished protein. According to Ester Neurosciences, attacking the finished protein stimulates the body to produce more AchE, triggering a battle between the drug and the nervous system. In contrast, the company says, Monarsen, which inhibits AchE synthesis, doesn’t cause this vicious cycle.

The company says that Monarsen could also have applications for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), a disease in which muscle-controlling nerve cells die.