Two recent publications from Pharnext describe a novel synergistic combination of 3 drugs (baclofen, naltrexone and sorbitol) and its effect on CMT1A both in the lab and in a phase II clinical trial. These 3 drugs already approved but for unrelated conditions, are combined at new optimal lower doses and under a new formulation. This novel potential therapeutic is called PXT-3003.
In preclinical studies, PXT-3003 was shown in vitro to synergistically increase myelination of axons cocultured with CMT1A rat Schwann cells. The combination of drugs was also shown to lower PMP22 expression (which at high levels in CMT1A is responsible for dysmyelination and consequently axonal loss and muscle atrophy). In the rat model of CMT1A different measures of effectiveness suggested that PXT-3003 was also promising and likely efficacious. The very low doses of all three components would also negate any adverse side effects.
The phase II clinical trial used three dose levels of PXT-3003 in 80 adults with mild to moderate CMT1A. The trial confirmed the safety of the combination drug and the best improvement was seen at the highest dose. PXT-3003 was safe and well tolerated. PXT-3003 showed, beyond stabilization, a significant improvement in the Overall Neuropathy Limitation Scale (ONLS) versus the placebo group. ONLS is a major scale to evaluate disability of upper and lower limbs for peripheral neuropathy. This represents the most promising potential treatment to date after ascorbic acid (vitamin C) failed to demonstrate efficacy for CMT1A in various clinical trials.
There are still gaps in understanding the mechanism of how PXT-3003 actually exerts its effect. It is hoped that by looking at patients over a longer period and possibly treating them earlier before the disease clinically affects them, this may improve nerve conduction and potentially halt and reverse disease. PXT-3003 represents a new hope for CMT1A patients in years, but there is still a long way to go (several years) before it may be more widely available as an FDA and EMA approved treatment for CMT1A.
An International Phase 3 trial will enroll later this year both in the US and Europe.
If you are interested in participating in the clinical trial, join the Global Registry for Inherited Neuropathies (GRIN).
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I have CMT, can I signup for the news letter and any clinical trial’s. I live in Missouri. Thanks.
Hi Dan,
Yes, I can add you to the newsletter list. Please visit https://www.hnf-cure.org/clinicaltrials/ for info about clinical trials.
I have Charcot-Marie-Tooth 1A, I live in Israel.. Where can I sign up for clinical
Trials?
I have identical twin girls who are 12 and diagnosed with cmt1a. How would we get involved?
Johanna,
Please reach out to me and we talk about how to get involved. There are many ways you can help spread awareness for CMT1A. [email protected]
My son is 13 and is positive for CMT1A we live in Brisbane Australia please keep me updated
I have Charcot-Marie-Tooth, I live in California. Where can I sign up for clinical
Trials?
Please visit https://www.hnf-cure.org/clinicaltrials/ for information.
I would love to go on this trial. I wonder what the chances are in Ireland ?
Was there some tests made with the PXT-3003 on CMTX patients?? I have this version of the disease so i have some hope for a treatment.
My son 15 has CMT1A and we are very interested in joining the trial. He just won the national sailing championship and is doing a lot of physical exercise in order to keep up. Should he just sign up on the list as above?
Hi Morten, that’s wonderful that your son is active and won a sailing championship! Thanks for sharing. Pharnext’s Phase 3 clinical trial for CMT1a is now open for screening and enrollment. You can find the open clinical sites marked in red on the HNF Centers of Excellence section of the HNF site. https://www.hnf-cure.org/centersofexcellence/
I would be willing to try the the drugs after a medical review because I also have COPD and coronary artery disease, have 3 stents in my arteries now
Please sign me up for CMT newsletter…thank you
Hi Janet,
You are scheduled to receive our newsletters!
Best,
Courtney
I am interested in trying this new drug combination for my CMT1A.
Excellent! Be sure to join GRIN at http://www.neuropathyreg.org to be informed of recruitement scheduled for later this year. Thanks for the post. Allison Moore, HNF CEO
Hi,
I live in Sherbrooke, Canada.
Is there any way I can participate to the clinical trial?
Will participants be accepted if they are on opioid pain medication currently?
Is there any way someone living in Canada can participate in this clinical trial
Where in Canada do you live?
I live in Vancouver, BC and am interested in participating
Great! Please join Global Registry for Inherited neuropathies https://neuropathyreg.patientcrossroads.org/