Introduction to NervGen and NVG-291 (Video)

[Mitchitsu]

Hi Luna, there is a TON of information and discussion about NervGen and nvg-291 over on Reddit. If you don’t have (or want) an account you can still download the app, search on those two words, and read lots and lots of discussion.
It tempered my expectations but not my excitement.

I spend a lot of time on Reddit. It is very good for certain types of conversation/information. But don't let it discourage you. They know nothing more than anyone else at this point.

[lunasicc42]

I spend a lot of time on Reddit. It is very good for certain types of conversation/information. But don't let it discourage you. They know nothing more than anyone else at this point.

this one?

NervGen : NervGen_NerveRepair (reddit.com)

[skippopotamus]

This might be worth a trip to Chicago. I definitely fit the criteria...

Haaa! I thought of you when I read the criteria. It seems like it will be hard to find 20 people with that specific combo of injury and incompleteness.
Be our inside person Mitch! You’re our mole!

[Mitchitsu]

Haaa! I thought of you when I read the criteria. It seems like it will be hard to find 20 people with that specific combo of injury and incompleteness.
Be our inside person Mitch! You’re our mole!

No joke, I'm 100% going to look into this a lot. I'm going to see if I can speak with them about doing it. Leaving my kids for a couple of months would suck but it would totally be worth it.

And I'll set up a separate place (since the admins won't allow it here to run a private blog )

Edit - although getting hit with a placebo would be absolutely awful. I would hope after the study if there is any efficacy, they would allow the people that got the placebo to have the treatment.

[Mitchitsu]

I might have missed it but is there a list of all the inclusions and exclusions? I would really like to look at it. I don't see it on the clinical studies page yet. Thanks in advance.

Edit: Please disregard. It looks like it was not officially put out yet. However, can somebody that is a lot more intelligent than me (should not be difficult to find here) Please explain what this means as if they were speaking to a 5-year-old

""evidence of electrophysiological sparing in two muscles the flexor digitorum and tibialis anterior""

Thank you guys very much,

[ActionXPotential]

In short the idea is that they want to be able to verify that there is "some" residual spinal tract or pathway leading from the brain to those muscles. There are relatively large regions of the brain designated to those muscles and can be found in stereotypical locations on most people. If you apply a magnetic or electrical discharge over those regions (through the skull dont worry its non invasive, gives a little tickle but thats about it), that signal will propogate from the brain to those muscles.

In some people with SCI this sparing is evident by your ability to slightly contract your arm and leg muscle, even if only a little bit, and even if only detectable using EMG. In other people who cannot, often times zapping these regions of the brain can provide evidence that there are spared spinal tracks even if you cannot voluntarily move it yourself. From a scientific standpoint im not sure if this is a primary outcome or not, or just being used for inclusion/exclusion. If this is used as a primary outcome it provides quantifiable and evidence that is continuous that if pre-treatment zap makes small response, and post-treatment zap makes larger response, then treatment must have worked. This is a bit of a different take compared to most prior clinical trials that focus on things as robust as quality of life improvements, where a treatment could have actually worked but not enough to make a difference in quality of life. Or measurements like Functional Independence which looks at the ability to do things you couldnt do before. Even more complicated tasks like manipulating objects or weight supported stepping are relatively complicated.

Unfortunately the FDA seems to rely on use of 1 pre-defined endpoint as a measure of success. If the investigators choice is something that could be a high bar, or not sensive enough like AIS grade or functional independence measures, then even if a treatment helped, if those tests didnt show statistical significant difference then the trial was deemed a failure. These electrophysiological measures may potentially be more sensitive. Some can argue that sensitivity isnt good if it doesnt actually improve QOL, but at the same time how many treatments have failed at clinical trials because we werent sensitive enough? Thats a philosophical debate for another day.

If this electrophysiology is being used as an inclusion/exclusion only, that also makes sense if the primary measures involve looking at "improvements" rather than "return" of function. Its easier to see a population have a 10 or 20% improvement in hand function than it is to see "maybe" 1/10 people have some function return. If those spinal pathways are damaged completely the bar for improvements are much higher.

Unfortunately with the FDA being so strict, the primary endpoint must be defined before beginning the study. So even if your hand/arm functions dont return but if something like bowel/bladder/sexual functions do, the trial can be considered a failure. Its an odd thing that us in the research world all recognize as a bit bogus and are advocating for change from the FDA. I think perhaps this first Phase 2 study could potentially help steer a more detailed phase 3 trial with how the results turn out. Are electrophysiology measures a good measure for a phase 3 trial? Should we be relying on AIS conversion scores? Should we be relying on improvements in quality of life or functional independence? Should we be evaluating hand dexterity or overground walking? Did something unexpected happen like return of bowel/bladder control and should we re-direct to that? The challenges with moving out of a mouse/rat and into humans are enormous, but when a phase 3 clinical trial can be literally 300-400-million $ + its important to set the trial up the best we can for success, because no investors will want to repeat that experiment due to choosing the wrong primary outcome measure, or choosing too variable of a population, etc.. There is a lot on the line!

[Mitchitsu]

Wow!!! Thank you so much for that incredible explanation. I was not expecting anything near that level of detail.

I'm able to flex those muscles as well as close my hands, move my fingers, and lift my ankles (although not a full range of motion with my ankles I can walk / take steps) So hopefully that won't be an issue. Although it's a lot easier to feel a flex in the calves than it is the shins, I do feel both a decent amount.

Everything else you mentioned is extremely thought-provoking and very much appreciated.

Thanks again for taking the time to explain things like that.

Edit: reading over what you wrote again, I hope the amount of function I have in those muscle groups does not create an exclusion for me with the study. Unfortunately I have been excluded from studies that I thought would be very helpful for me before because they said I was "too functional"... Which is pretty funny in an ironic and depressing way considering how much help I need with things in life.

[Norm]

I just can’t believe I’ve been paralyzed going on 41 years now and there still is not one thing out there to improve my life. 😰

[LethalSpoon]

Yeah, it s***s. Sadly, CNS is too complex, and we dont have the tools or knowledge to understand it at the level is required to solve SCI puzzle. Neuroscience is too young, and SCI is a very small niche.

[stephen212]

I hear you and feel you (well the parts of me that still have sensation, anyway). I'm almost at the 40-year mark and the strides in deliverable therapies over that span has been close to zilch. I long ago gave up waiting or hoping for a cure. For me, the smaller but extremely significant victories of managing my neurogenic bladder (with Botox) and bowel (with Peristeen) have been life-changing. Walking, however, will have to wait for my next incarnation. Not happening again on this present ride.

[Norm]

Peristeen works good?

[steve nguyen]

It would be nice if all current clinical trails have good results for treatments in the year of 2024 !!!

[comad]

Hope to see soon some posts about increased speed of trial preparation or post trial data analysis due to AI tools inclusion.
Time is comfort zone of healthy & young and rich scientists. Urgency is our cry that we are trying to supress daily.

[Sparky831]

https://www.newsfilecorp.com/release/166073

[lunasicc42]

NervGen Pharma Reports Q1 2023 Results and Provides Operational Update Including Clinical Trials of Proprietary NVG-291 - NervGen Pharma