Early treatment of CMT disease
Inventors
Cohen, Daniel • Chumakov, Ilya • HAJJ, RODOLPHE • Milet, Aude • Nabirochkin, Serguei • Nave, Klaus-Armin • Prukop, Thomas • Sereda, Michael
Assignees
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Publication Number
US-12226413-B2
Publication Date
2025-02-18
Expiration Date
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 provides a method of treating Charcot Marie Tooth type 1A disease (CMT1A) in a subject bearing a duplication or mutation of a PMP22 gene by administering a combination of baclofen, sorbitol, and naltrexone, or a pharmaceutically acceptable salt thereof. The method targets human subjects at an early stage of disease, including a human of 7 years of age or less, and in whom the subject is showing no or few physiological or morphological signs of CMT1A.
The method is characterized by a long term reduction of a sign, symptom, or clinical manifestation of CMT1A for at least 1 year. The described support includes in vivo transgenic PMP22 rat data showing early functional improvements that persist after treatment cessation.
The described effects include improved electrophysiology and nerve myelination or morphology, as well as functional and morphometric measures such as grip strength, inclined plane performance, distal motor latency, axon caliber distribution, and normalized G-ratio. The approach also includes a patient stratification and outcome-measure framework using CMT neuropathy score (CMTNS), CMT neuropathy score 2 (CMTNS2), Charcot-Marie-Tooth disease pediatric scale (CMTPedS), and Overall Neuropathy Limitations Scale (ONLS).
Claims Coverage
The independent claim is directed to treating CMT1A in a young human bearing a PMP22 gene duplication or mutation using baclofen, sorbitol, and naltrexone, with early-stage patient selection and a requirement for long-term reduction lasting at least 1 year. The inventive concept includes at least 1-year long-term reduction of signs, symptoms, or clinical manifestations in an early-stage, young subject showing no or few physiological or morphological signs of CMT1A.
Treating CMT1A in an early-stage young human with PMP22 duplication or mutation
A method of treating Charcot Marie Tooth type 1A disease (CMT1A) in a subject bearing a duplication or mutation of a PMP22 gene by administering a combination of baclofen, sorbitol, and naltrexone, or a pharmaceutically acceptable salt thereof, effective to treat CMT1A; wherein the subject is a human of 7 years of age or less; is at an early stage of the disease; and is showing no or few physiological or morphological signs of CMT1A.
Long-term reduction of clinical manifestations for at least 1 year
The method provides in said subject a long term reduction of a sign, symptom, or clinical manifestation of CMT1A for at least 1 year.
Overall, the claim coverage centers on early intervention in a young human (≤7 years) with PMP22 duplication or mutation who shows no or few physiological or morphological signs, using baclofen, sorbitol, and naltrexone to achieve a long-term reduction of CMT1A signs, symptoms, or clinical manifestations lasting at least 1 year.
Stated Advantages
Long term reduction of a sign, symptom, or clinical manifestation of CMT1A for at least 1 year after early-stage administration.
Unexpected long-term delay or prevention of clinical manifestations after transient early dosing [as supported by described long-lasting functional improvements].
Improved electrophysiology and nerve myelination or morphology, including normalized G-ratio and axon caliber distribution.
Documented Applications
A method of treating Charcot Marie Tooth type 1A disease (CMT1A) in human subjects bearing a PMP22 gene duplication or mutation, particularly in early-stage pediatric subjects showing no or few physiological or morphological signs.
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