Treatment for Rare Hereditary Muscle Disease Shows Promise

Drug that treats GNE myopathy (GNEM) causes improved muscle strength in upper extremities.

An extended-release sialic acid supplement has shown significant potential to treat patients with GNE myopathy (GNEM) during a clinical study.

GNEM is a rare and progressive adult onset muscle disease where patients have distal muscle weakness, such as foot drop. It eventually spreads to the upper extremities, which leads to the loss of the ability to walk.

Patients who suffer from GNEM have mutations in a gene controlling a key enzyme in the synthesis pathway for sialic acid (SA).

The phase 2 double-blind study used 2 dosages of aceneuramic acid extended release (Ace-ER) tablets in formulations of 3 g/day and 6 g/day on 47 randomized patients. The first group was administered a dosage of 3g a day for 24 weeks. The second was administered 6g a day, and the third group was given a placebo.

Placebo patients were switched to either the 3 g/day or 6 g/day dosages after 24 weeks, and the other groups continued the same dosages.

The results of the study showed that patients administered Ace-ER therapy saw a dose dependent increase in serum sialic acid levels. Patients administered 6g/day dosages were found to retain muscle strength in their upper extremities after 24 weeks of therapy compared with patients in the placebo group.

The 6 g/day dose compared to the 3 g/day dose experienced a maintained effect on the upper extremities over 24 weeks.

Although there was a similar dose dependent trend found in the lower extremities, it did not achieve statistical significance.

"In summary, this is the first evidence in humans that SA supplementation may affect the progression of muscle weakness in GNEM," said lead investigator Zohar Argov, MD. "This Phase 2 study included subjects at various stages of the disease including those who were advancing to a wheelchair-bound state. The findings suggest that initiating treatment earlier in the disease course may lead to better outcomes. It is our hope that the Phase 3 trial will result in the first therapeutic agent for this condition."