VGSDs: a potential breakthrough on the horizon for neuropathy pain?

Posted by HankB @jesfactsmon, Mon, Jun 22 7:35am

Hi, I started this discussion to talk about hope for a cure for neuropathy pain. Soon after my wife developed peripheral neuropathy from chemo in 2014 I found out some information that I was very interested in and excited about at that time and, having followed the progress since then, still am even now. It involves a new non-addictive drug therapy for PN pain which is currently in development that has no opioid like side effects.

Some of you may already have read something about this. For me it started when I read an article online which talked about a toxin from a fish know as the pufferfish called tetrodotoxin (TTX). The pufferfish is a delicacy in restaurants in Japan and has to have the toxin removed by an expert or it could kill the restaurant patron. I found out that TTX may hold the key to solving neuropathic pain. I read as much as I could find back in 2014 and 2015 about this substance. There is a company named Wex Pharmaceuticals which was developing a PN drug back then based on TTX. It was in phase III trials as a potentially life altering solution for PN sufferers. I was so excited I wanted to know what its chances were, and I actually managed to contact a representative from Wex who told me back then that the chances of there being an actual drug on the market as a result of these trials was iffy at best and possibly years away. Later I found out that a drug name selected for it back then was Tectin.

Having heard from the horse's mouth (so to speak) that this thing was not likely to happen soon I quit thinking about it until a few months ago when I happened upon an article online by The Scientist magazine. It contained some info I did not know before as to what TTX actually does to relieve pain. I found out that TTX is what is known as a "voltage gated sodium channel" (VGSD) blocker. The picture I included (hopefully it shows up) is of several VGSDs (in purple) along a neuron.

As I understand it, VGSDs are channels located on the surface of nociceptors (pain neurons) through which nociceptors get their pain responses triggered. In humans there are 9 different VGSDs and the one that has a direct relationship with PN pain is called NaV1.7 which is generated by the SCN9A gene. There are a variety of substances that effectively block NaV1.7, which stops the pain of PN. One of the best of these is cocaine. Unfortunately, things like cocaine don't just block NaV1.7 but they block some of the other 8 VGSD's as well and that is not good. Because the other VGSD's are responsible for other functions in the body which you would not want to stop, like heart function, etc. Now after Wex pharmaceuticals were in phase III trials with Tectin they did not have good luck with it apparently and they shut down that trial. However I have found out that Wex has another ongoing trial with a followup effort called Halneuron. That drug has recently been in phase II trials for cancer related pain such as chemo induced peripheral neuropathy.

Now Halneuron may or may not eventually become a viable FDA approved drug treatment. But I believe from what I have read that there is a significant scientific research effort ongoing by various companies to find something to block the NaV1.7 VGSD and not block the other 8 VGSD's at the same time, thus causing relief from pain for PN sufferers without jeopardizing their health in other ways. A company called Chromocell is also researching a drug (named simply CC8464) based on VGSDs and was entering phase II trials with it as of September 2019. There may be other companies working on VGSD blockers as well.

The article which I mentioned earlier from The Scientist is from 2017 and explains really clearly how the NaV1.7 VGSD functions and what has been done to determine how this might eventually develop into a breakthrough solution for PN. Here is the link to that article for those interested:
https://www.the-scientist.com/features/targeting-sodium-channels-for-pain-relief-30147
Just wanted to tell you guys about this so you are aware of this avenue of hope. It's nice to know somebody is working on SOMETHING that might help people with this ridiculous affliction of PN! VGSD research has been ongoing for many years (at least since 2006) and I have personally been waiting for it to develop into a useful drug for 6 years. I have not heard anything more recent that Sept. 2019 about the current status of any of these drug trials but do hope for some good news before too long.

And finally, if anyone reading this knows anything further that they can add about this research or these drug trials, please let me know. I'd be very interested. Thanks, Hank

VGSD

Thanks for starting this new discussion @jesfactsmon. Sounds like voltage gated sodium channels (VGSD) could hold some promise to help people with neuropathy pain. Not so sure about the puffer fish toxin but maybe that's just me and the visual pictures I have in my mind 🙂 Here's some research information I found on Google Scholar (https://scholar.google.com/).

Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain:
https://www.mdpi.com/2227-9717/8/6/680

Structure and Pharmacology of Voltage-Gated Sodium and Calcium Channels:
https://www.annualreviews.org/doi/abs/10.1146/annurev-pharmtox-010818-021757

Liked by rwinney, HankB

REPLY
@johnbishop

Thanks for starting this new discussion @jesfactsmon. Sounds like voltage gated sodium channels (VGSD) could hold some promise to help people with neuropathy pain. Not so sure about the puffer fish toxin but maybe that's just me and the visual pictures I have in my mind 🙂 Here's some research information I found on Google Scholar (https://scholar.google.com/).

Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain:
https://www.mdpi.com/2227-9717/8/6/680

Structure and Pharmacology of Voltage-Gated Sodium and Calcium Channels:
https://www.annualreviews.org/doi/abs/10.1146/annurev-pharmtox-010818-021757

Jump to this post

Thanks John, One other note, apparently the toxin is used to produce an effect on one of the 4 "petals" on the VGSD which causes the pore in the center to shut which stops the channel from allowing the entry of sodium, the catalyst for the pain response. Also, I forgot to mention that there are other creatures beside pufferfish from which this TTX toxin can be extracted such as

Gastropod mollusc.
The eggs of horseshoe crabs.
Newts of the genus Taricha.
The skin of Atelopid frogs.
The skin and viscera of porcupine fish, globefish, balloon fish, blowfish, sunfish, toadfish, blue-ringed octopus, and some species of salamanders.

I think I also read tarantula (or perhaps black widow) spiders, can't remember which.

REPLY
@jesfactsmon

Thanks John, One other note, apparently the toxin is used to produce an effect on one of the 4 "petals" on the VGSD which causes the pore in the center to shut which stops the channel from allowing the entry of sodium, the catalyst for the pain response. Also, I forgot to mention that there are other creatures beside pufferfish from which this TTX toxin can be extracted such as

Gastropod mollusc.
The eggs of horseshoe crabs.
Newts of the genus Taricha.
The skin of Atelopid frogs.
The skin and viscera of porcupine fish, globefish, balloon fish, blowfish, sunfish, toadfish, blue-ringed octopus, and some species of salamanders.

I think I also read tarantula (or perhaps black widow) spiders, can't remember which.

Jump to this post

Hank, my big hope for future patients is a method, treatment or therapy that reverses nerve damage instead of just treating the symptoms which to me is better. Just my humble opinion and hope for all you pain warriors 🙂

Liked by avmcbellar, HankB

REPLY
@johnbishop

Hank, my big hope for future patients is a method, treatment or therapy that reverses nerve damage instead of just treating the symptoms which to me is better. Just my humble opinion and hope for all you pain warriors 🙂

Jump to this post

Absolutely! But while we wait for that it would be nice to be able to take something that actually stopped the pain, was not addictive and had few side effects. That just doesn't seem to exist at the moment.

REPLY

Thank you for sharing this information, @jesfactsmon If it would work, I wouldn't care what fish or critter it comes from. Maybe I should go to Japan and eat some of those pufferfish.

Jim

REPLY
Please login or register to post a reply.