If the management of type 1A Charcot-Marie-Tooth disease (CMT1A) is symptomatic (physiotherapy, orthopedic surgery, etc.), several molecules have been evaluated or are still being evaluated during clinical trials. A team from the âFamilial amyloid neuropathies and other rare neuropathies (NNERF)â reference centre reviews the therapeutic avenues targeting this hereditary neuropathy:
- IFB-088, developed by Inflectis Bioscience, with the support of AFM-Telethon: a first trial in healthy volunteers has shown good tolerance of the product. A phase II trial in patients with CMT is in preparation.
- PXT 3003 (a combination of baclofen, naltrexone and sorbitol), developed by Pharnext, with the support of AFM-Téléthon: phase II (in France) and phase III (international) trials evaluated the drug candidate, with encouraging results in terms of tolerance and efficacy. A new international phase III trial is planned to confirm these results on a larger scale.
- A gene therapy product based on the neurotrophin 3 gene and developed by Nationwide Childrenâs Hospital (Ohio, United States): a phase I / II trial is planned in the United States.
- ADX71149 (GABAB PAM), developed by Addex Therapeutics: the product is still in the preclinical development stage.
- Several molecules have seen their development halted for lack of efficacy (ascorbic acid) or for the risk of toxicity (ulipristal acetate and FLX-787).
What about the future?
The authors highlight two promising therapeutic approaches:
- Antisense drugs (antisense oligonucleotides or small interfering RNAs), already successfully prescribed in other neuropathies such as hereditary transthyretin amyloidosis, are being studied preclinically in CMT1A to target the PMP22 gene, duplicated in CMT1A.
- Heat shock protein activators or macrophage activating factors may act on the toxic buildup of PMP22 in Schwann cells.
