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).
I think my 17 year old son may have this. We began to notice “problems” in 7th grade but didn’t know what was wrong. We have been told his hip flexors are too tight. In the past few years I have noticed his feet (toes particularly) were “crunching up”. His feet look like the pics I have seen on many sites about CMT. Please sign me up for the newsletter.
How soon an where can I get it?
My husband at age 76 just received a diagnosis. Please send the newsletter!
Hi Lynn,
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My husband has been to many nurologists over the years and we finialy found one who would not only listen to him but did a very good exam and took the time to do family history. We can not do the DNA test because insurance will not say if they will cover the cost until after it is done! But the doc is pretty sure he has CMT but does not have the high arch his foot does clap when he walks and is getting worse. His neuropathy has spread to his knees and in his arms and back some. I am not sure where you are located or if he could even get into the trial without the DNA test first. We live just south of Tulsa OK ad would like more information on this please. Thankd
My husband and sons have CMT 1A. My husbands mother , and his sister as well. Could you please sign me up for the newsletter.
Hi Cynthia,
You are all signed up. You should be receiving emails now.
Best,
Courtney
please sign me up.. thank you.
Hi April you are signed up to receive HNF’s newsletters.
I don’t now which type or phase I am in.I live in Rockford Illinois.I heard the test are really expensive to know which type I have.I am 66 years old and on SS and 2 supplements insurance cards.I am still able to get along with a walker.Where is the closest place I could go?I also have COPD.Will Insurance pay for this treatment?
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You are all signed up! Thank you
Please sign me up for your newsletter so I can stay on top of any new developments.
Thank you.
Hi Ernest,
I have signed you up!
Thanks,
Courtney
Hi Courtney,
Please sign me up for the newsletter.
Thanks,
Mohammad
You are signed up!
Thanks,
Courtney
Sign me up! I am interested in PXT3003 treatment.
Thank-you
Ron
Would this or any other trial be open to someone with CMT type 1B? My family has multiple members with this condition.
My husband and multiple generations in his family have CMT1A. We had gene testing to determine this. Please send me your newsletter as we are very interested in treatments since our 5 year old grandson has now been diagnosed. Do you know if stem cell platelet treatment is helpful?
Hi Susan,
I have signed you up for our newsletter. Do you like near a HNF center that is offering the clinical trial for CMT1A? https://www.hnf-cure.org/centersofexcellence/
I was born and raised in Honolulu Hawaii and am unaware of anyone else on my island who shares this disease of CMT. I would’ve to be a candidate for clinical trials, and to receive the newsletter. Thank you for providing assistance, information, and hope.
Pls. Sign me up for newsletter
Hi Christopher,
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Which year shall we hope there will be a treatment for cmt !!
What is the next step of pxt 3003 … is the third stage is the last stage !!!
I live in Stockholm, Sweden and wonder if I can participate in the trials?
I also would like to recieve the newsletter, can you sign me up? Thanks.