Low dose naltrexone for Charcot Neuropathy

pattismith

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Novel Drug Cocktail Offers Rare Neuropathy Patients New Hope

— Charcot-Marie-Tooth patients see improved outcomes with repurposed drugs


by Judy George, Senior Staff Writer, MedPage TodayMay 8, 2019

The investigational combination of baclofen, naltrexone, and sorbitol known as PXT3003, given as a twice-daily oral solution, offered the first evidence of meaningful improvement for patients with Charcot-Marie-Tooth type 1A, said Florian Thomas, MD, PhD, of Hackensack University Medical Center in New Jersey, at the Emerging Science session of the 2019 American Academy of Neurology annual meeting.

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The polytherapy has multiple mechanisms of action, according to drug maker Pharnext: a synergistic inhibition of PMP22 gene overexpression associated with myelination improvement, direct nerve protection, and positive effects on muscle cells, neuromuscular junctions, and immune

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Dose 3 was 6 mg baclofen, 0.70 mg naltrexone, and 210 mg sorbitol; dose 4 was twice as much as dose 3. Both doses were given twice daily for up to 15 months.

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Over 12 to 15 months, patients in the dose 4 group improved while the "placebo [group] deteriorated, as expected,"


 

pattismith

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How dose the sorbitol work? Generally used as a sweetener or to treat consipation?
While Baclofen and naltrexone have already shown interest in fibro/me, I doubt that Sorbitol has any interest outside CMT1A.

sorbitol accumulation already showed neurotoxicity in CMT2 and is believed to contribute to diabetic neuropathy so I wouldn't take this one
Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes



Sorbitol adjunction seems useful to downregulate PMP22, which is what we need for CMT1A, but I'm not convinced that we need this in any other neuropathy...
 

heapsreal

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While Baclofen and naltrexone have already shown interest in fibro/me, I doubt that Sorbitol has any interest outside CMT1A.

sorbitol accumulation already showed neurotoxicity in CMT2 and is believed to contribute to diabetic neuropathy so I wouldn't take this one




Sorbitol adjunction seems useful to downregulate PMP22, which is what we need for CMT1A, but I'm not convinced that we need this in any other neuropathy...
The naltrexone may reduce tolerence to baclofen, although its low any.
I tecall dosing for alcoholics was 25mg tid.thats a hefty dosecwhich i tried and no issues coming off although i did a quicker taper.
 
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So has anybody actually tried this combination?
I'm concerned about the baclofen because of the nervous system rewiring. Having experienced benzodiazepine withdrawal that in itself is enough to permanently rewire your system.
 

Hoosierfans

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Wow this is an interesting combo and will discuss it with my new neuroimmunologist. My notes on Baclofen is that a starting dose should be about 5 mg. It does have a withdrawal syndrome associated with it. It works on both Gaba B receptors and dopamine.