Compositions for treating CMT and related disorders
Inventors
Cohen, Daniel • Nabirochkin, Serguei • Chumakov, Ilya
Assignees
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Publication Number
US-10905686-B2
Publication Date
2021-02-02
Expiration Date
Abstract
The present invention relates to compositions and methods for the treatment of the Charcot-Marie-Tooth disease and related disorders.
Core Innovation
The patent describes a pharmaceutical composition for treating Charcot-Marie-Tooth (CMT) and related disorders, including CMT1A, toxic neuropathies, and ALS. The composition includes baclofen or a pharmaceutically acceptable salt, sorbitol or a pharmaceutically acceptable salt, and naltrexone or a pharmaceutically acceptable salt as active ingredients, together with a pharmaceutically suitable excipient or carrier.
The disclosed compositions use defined baclofen and naltrexone amount ranges in combination with sorbitol, and include ternary and combinatorial drug regimens built around baclofen and sorbitol, including baclofen+sorbitol+naltrexone. The disclosure further discusses PMP22 modulators and myelination-related markers such as MBP expression and pmp22 RNA expression.
The patent reports experimental findings consistent with modulation of PMP22 and myelination, including in vitro reduction of PMP22 and restoration of myelination markers, including MBP, with drug mixtures such as Mix7 containing (R/S)-baclofen, d-sorbitol, and naltrexone. In vivo, the patent reports improved behavioral performance in CMT transgenic rat models together with decreased pmp22 RNA expression, and describes protective outcomes in oxaliplatin-induced neuropathy and an ALS (SOD1G93A) rat model.
Claims Coverage
The independent claims define three inventive features: a pharmaceutical composition, a unit dosage form, and a patient pack. Across these claims, the main inventive feature is a ternary baclofen, sorbitol, and naltrexone formulation using defined dosage ranges and oral liquid packaging concepts.
Ternary baclofen-sorbitol-naltrexone pharmaceutical composition in defined baclofen and naltrexone ranges
A pharmaceutical composition comprising baclofen or a pharmaceutically acceptable salt thereof in an amount between about 1 and about 300 μg/kg of a human subject; sorbitol or a pharmaceutically acceptable salt thereof; naltrexone or a pharmaceutically acceptable salt thereof in an amount between about 1 and about 100 μg/kg of the human subject; and a pharmaceutically suitable excipient or carrier.
Ternary baclofen-sorbitol-naltrexone unit dosage form in defined baclofen and naltrexone ranges
A unit dosage form comprising baclofen or a pharmaceutically acceptable salt thereof in an amount between about 1 and about 300 μg/kg of a human subject; sorbitol or a pharmaceutically acceptable salt thereof; naltrexone or a pharmaceutically acceptable salt thereof in an amount between about 1 and about 100 μg/kg of the human subject; and a pharmaceutically acceptable excipient or carrier.
Patient pack with an oral liquid formulation of ternary baclofen-sorbitol-naltrexone and optional instructions
A patient pack comprising a liquid formulation for oral administration, comprising a composition comprising baclofen or a pharmaceutically acceptable salt thereof in an amount between about 1 and about 300 μg/kg of a human subject; sorbitol or a pharmaceutically acceptable salt thereof; naltrexone or a pharmaceutically acceptable salt thereof in an amount between about 1 and about 100 μg/kg of the human subject; a pharmaceutically acceptable excipient or carrier; and, optionally, instructions for administration of the liquid formulation.
Across the independent claims, the patent claims ternary compositions and product formats that include baclofen, sorbitol, and naltrexone with defined baclofen and naltrexone μg/kg ranges, further covering a unit dosage form and a patient pack that includes a liquid formulation for oral administration and can include optional administration instructions.
Stated Advantages
Improved behavioral performance in CMT transgenic rat models.
Decreased pmp22 RNA expression in CMT transgenic rat models.
In vitro reduction of PMP22 and restoration of myelination markers (MBP).
Protection in oxaliplatin-induced neuropathy.
Reported protection in an ALS (SOD1G93A) rat model.
Documented Applications
Treating Charcot-Marie-Tooth Disease Type 1A (CMT1A) in a human subject, including administration once, twice, or three times daily.
Protective use in oxaliplatin-induced neuropathy.
Protective use in an ALS (SOD1G93A) rat model.
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