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**LethalSpoon** · 7 Jun 2022, 12:48 PM

At this stage, I dont think is possible to rate what therapy is better or superior. All of the treatments are only proven in mice, and almost everything you throw to their injured spinal cord can make those tinny bastards recover and walk

**Maxahoy** · 7 Jun 2022, 9:13 PM

Having looked in cursory detail at the academic paper this news release focuses on, I don't think this is currently showing any promising signs for us chronic SCI patients. It will, however, be promising for new incomplete patients. Particularly since it appears to prevent secondary injuries to the spinal cord from inflammation or secondary axon death in the days after injury. While I don't have a link to the article behind the paywall, that's my understanding. I have also seen comments from researchers on the reddit forum /r/SpinalCordInjuries who have suggested the same -- this treatment will be most effective for new injuries and offers less promise for chronic patients. Don't mean to dash hopes, just trying to inject some realism. When I was in the hospital after my injury this past February I was sent this study multiple times, and the university wifi was able to bypass the paywall.

**ActionXPotential** · 8 Jun 2022, 9:26 AM

Dr. Stupp recently did a pod cast talking about this on CureCast.

https://soundcloud.com/user-612244013

see episode 60.

In short, most of the data is technical jargon about the development of their bio-material that nobody besides bio-material engineers could probably make sense of. The application to SCI was all acute, however the magnitude of reported effects was quite large (in the podcast Dr. Stupp specifies it really mainly applies to acute SCI for now but obviously chronic stage stuff is not off the radar for future experimentation). They had huge sample sizes (n=20-30 from what i can remember, usually its 6-12), which instills confidence in the reproducibility of findings. They used a very, very, severe model of SCI so seeing as large of behavior effects as they did was pretty cool stuff, but at the present moment it is all proof of principle.

I think of the article more as another scientific advancement in biomaterials than anything else. In concept the novelty of the material is that it seems to act as a molecular stir bar to increase the "mixing effect" of other growth factors/proteins embedded in the material with the host tissue. the mixing effect increases the potency of the growth factors likely by increasing the frequency that the growth factors find their target receptors in the cord. From a scientific standpoint this is brilliant and exciting and definitely has potential to be used in chronic SCI in several ways. From a translational standpoint, and this is just my opinion, we are still a very long way off from seeing this matriculate into people and here is why.

1) there is a lot of argument right now about whether or not growth factor-style treatments should be used for SCI due to a potential threat of making things worse. Much of the literature shows that trophic/growth factors can improve motor functions, but we also know based on a ton of basic science research that several of the mechanisms mediating functional improvements from trophic/growth factor therapies might also mediate maladaptive changes that would cause or exacerbate neuropathic pain, autonomic dysreflexia,and potentially exacerbate neurogenic bladder. The history of trophic/growth factor treatments is rich, and there really, actually, isnt much data to support the role of exogenous delivery of these compounds as exacerbators of pain, but the threat is there, it just remains an understudied area of basic research. Some individuals like Dr. Garraway at Emory in Atlanta are working on figuring this out but the science is complicated. Whether or not pain could get worse could depend on the location of injury, the severity of injury, other elements of the delivery approach etc. We simply dont know enough and unfortunately the threat is enough to stigmatize the idea of using these proteins as therapeutics in the eyes of many (and I mean many many) scientists. Hopefully we can figure this out for sure one way or another because from a motor recovery stand point, the effects have been large and reproducible over decades in animal models.

2) injecting a gel into a spinal cord comes with very real risk of doing further damage to the cord. In this study the authors used an injury model that doesnt leave much room for things to get worse then pumped the cords full of gel to an extent that looks quite damaging. In reality, most cases of SCI are incomplete, so injecting a large bolus of gel into a cord will cause tissue displacement which might cause more damage to tissue in situations when there otherwise would be surviving tissue. Unfortunately in the clinic, we dont know how severe an injury will be until its probably outside of the acute/sub-acute therapeutic window. Whether or not this stuff will work in chronic conditions is TBD, but prolonging this to chronic SCI comes with a whole different set of concerns about plasticity and potential pain-mediating effects in those stages of recovery. For the acute window, i, for one, see a ton of dangers in their approach unless they can find some way to apply this in a less damaging way (Sub-dural for example instead of intraspinal). Either way, the approach of injecting a bolus of gel into the cord could still be viable in less severe injuries, but the dosing and safety would likely need to be figured out first, as well as figure out how to predict who would be viable candidates in the acute window, of which we still dont have good ways to predict this in people.

Taken together its not damning to the prospects of things like this emerging in clinical use but there are many things to figure out first which could take quite some time.

While the injury model used was very severe, we cannot rule out the idea that their therapy was mainly neuroprotective. In their data this was indicated by observing sparing of neurons surrounding the lesion. While this is not bad for acute SCI, that particular mechanism has little implications for chronic SCI. We know that growth factors also can induce "plasticity" (the umbrella term for physical/chemical change in the nervous system that affects functions) but we know that this plasticity does not occur as readily in chronic SCI as it does acute SCI (this problem is the approach behind Nervgen). And we know that growth factors can induce regeneration into a permissive medium, which this therapy showed potential to do both (enhance axon growth and be a permissive medium), but the extent of regeneration into the graft was minimal. Unfortunately all of these mechanisms just have more potential in acute SCI than chronic SCI at this point. However, I will say that one of the bigger limitations to regenerative treatments in chronic SCI are the large cavities that form. Regenerating axons likely will not grow into a fluid filled cavity and therefore, filling that cavity with cell transplants or hydrogels (like this) is likely going to be needed for a profoundly effective regenerative treatment. Further, at the chronic stage of SCI we will know more who is and isnt viable candidates for the treatment and know more precisely where to put it and how much to put in, making the hydrogel tech highly applicable for chronic SCI conditions in a different way. If this strategy were to be applied to the chronic condition I would be surprised if the same magnitude of effect was observed. Potentially a small effect, maybe. But I am personally excited by the refinement of the technology that might enhance regenerative strategies in the chronic condition.

I personally feel as though this article got some misrepresentative, and potentially damaging, coverage by the news. It is good work, but the implications have been blown up irresponsibly.

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Injectable "Dancing" Molecules can repair SCI

Injectable "Dancing" Molecules can repair SCI

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