Early treatment of CMT disease

Inventors

Cohen, Daniel • Chumakov, Ilya • HAJJ, RODOLPHE • Milet, Aude • Nabirochkin, Serguei • Nave, Klaus-Armin • Prukop, Thomas • Sereda, Michael

Assignees

Pharnext SA

Abstract

The present invention provides methods for treating, preventing, or delaying the onset of Charcot-Marie-Tooth Disease type 1A (CMT1A), by administering to a subject in need thereof a combination comprising baclofen, sorbitol and naltrexone, or a pharmaceutically acceptable salt thereof.

Core Innovation

The invention relates to a method of treating Charcot Marie Tooth type 1A (CMT1A) disease in a subject bearing a duplication or mutation of a PMP22 gene. The method comprises administering to the subject a combination of baclofen, sorbitol, and naltrexone, or a pharmaceutically acceptable salt thereof, effective to treat CMT1A. The subject is a human of 2 years of age or less and is at an early stage of the disease.

The disclosed approach emphasizes prevention or delay of symptom onset and long-term functional and electrophysiological benefits after transient treatment. The description includes early-stage treatment in very young children and uses a PMP22 transgenic rat model to support that effects can persist weeks after stopping therapy. The reported functional and electrophysiological improvements include grip strength and inclined plane performance and electrophysiological parameters such as distal motor latencies.

The disclosed approach further reports improvements in nerve myelination and morphology, including axon caliber distribution and normalized G-ratio, persisting after therapy is discontinued. The document also provides patient selection criteria using CMT neuropathy score and related pediatric scales, including CMTNS, CMTPedS, and ONLS, and describes possible administration timing such as transient versus chronic administration. The combination and its components are described in terms of dosing, relative weight ratios, and possible use of pharmaceutically acceptable salts.

Claims Coverage

The independent claim covers the core treatment concept: administering a baclofen/sorbitol/naltrexone combination (or pharmaceutically acceptable salt) to a human subject (≤2 years old) with early-stage CMT1A associated with a PMP22 gene duplication or mutation. The inventive features are mainly directed to subject and disease stage limitations and the specific combination of drug components and formulation scope.

Overall, the claim coverage centers on early-stage treatment of very young human subjects with PMP22-linked CMT1A using a baclofen/sorbitol/naltrexone combination, including pharmaceutically acceptable salts.

Stated Advantages

Documented Applications