Editorial note: This post refers to Pharnext and its experimental CMT1A therapy PXT3003. Pharnext is no longer operating, and PXT3003 is not an approved or available treatment. We have kept this post as part of our historical record.

Two recent publications from Pharnext describe a novel synergistic combination of three drugs (baclofen, naltrexone, and sorbitol) and its effect on CMT1A, both in laboratory studies and in a Phase II clinical trial. Each of these drugs is already approved for other conditions. In this combination, they are used at new, optimized lower doses under a new formulation. The resulting investigational therapy is called PXT-3003.

In preclinical studies, PXT-3003 was shown in cell culture to synergistically increase myelination (the formation of the protective sheath around nerve fibers) in axons co-cultured with CMT1A rat Schwann cells. The combination also lowered expression of PMP22, the protein that, when overproduced in CMT1A, causes dysmyelination and the resulting axonal loss and muscle atrophy. Studies in a rat model of CMT1A further suggested PXT-3003 was promising and likely efficacious. Because all three components are used at very low doses, researchers believe adverse effects would be minimal.

The Phase II clinical trial tested three dose levels of PXT-3003 in 80 adults with mild to moderate CMT1A. The trial confirmed the safety of the combination and showed the best improvement at the highest dose. PXT-3003 was safe and well tolerated. Beyond stabilization, it showed a significant improvement in the Overall Neuropathy Limitation Scale (ONLS) compared to the placebo group. The ONLS is a standard scale used to evaluate disability of the upper and lower limbs in peripheral neuropathy. This result represents one of the most promising signals in CMT1A research since ascorbic acid (vitamin C) failed to demonstrate efficacy in earlier clinical trials.

Gaps remain in understanding the precise mechanism by which PXT-3003 exerts its effect. Researchers hope that studying patients over longer periods, and potentially treating them earlier before clinical symptoms appear, may further improve nerve conduction and possibly halt or reverse disease progression. While PXT-3003 represents renewed hope for people with CMT1A, several years of additional study are still required before it could be more widely available as an FDA- and EMA-approved treatment.

An international Phase 3 trial was planned to begin enrollment later in 2015, both in the United States and Europe.

If you are interested in participating in clinical trials for CMT, join the Global Registry for Inherited Neuropathies (GRIN).