I truly, truly hope this works as described, even partially, on humans. It is so frustrating to see someone who would be able to walk if only the signal could get to their lower extremities.
My grandfather is a paraplegic, and man how much I hope this isn't just faery dust.
Based on this stimulating Axon growth, it sounds like it might help to repair the damage caused by MS. That would be amazing news. Not a cure per se, but a way to actually treat symptoms rather than just surpressing. Worryingly, they mention a few neurodegenerative diseases but not MS.
BioNTech is working on a vaccine against MS that is supposed to untrain the immune system to no longer attack own tissue. It should at least slow progress of the disease and even seems to have allowed to reverse early damages in mice. Letâs keep our fingers crossed.
Through the years I've seen dozens and dozens of "cures" for "MS" in mice (I put MS in quotes because, at this point, I've grown skeptical that the induced encephalitis mouse model is all that helpful in predicting drug performance for humans with MS). The closest thing we have to a "cure" is actually a medication that's been on the market for a while, but it was used to treat certain types of blood cancer before they discovered that it works really well for MS too.
It's now available generically: Rituximab. There's another hack that Genentech was able to patent and approve for MS to produce Ocrelizumab, which does the same thing as Rituximab but costs an order of magnitude more. Because that's how the world of big pharma works.
In essence, wiping out your plasma cells (a.k.a. B cells or lymphocytes) seems to stop MS in its tracks. Where my neurologist would typically see 2 or 3 new lesions in any given patient per year, instead now my neurologist is seeing 2 or 3 new lesions per year in the population of all their RRMS patients who are on Rituximab (or Ocrelizumab). And it turns out the immune system can get along pretty well with all the other cells types it has, such as T cells.
Just noting that -mab therapeutics are not synthesized directly, they are produced in cloned cell lines. Itâs practically impossible for one pharma company to replicate another companies -mab, since they will never have access to the exact cell line used to manufacture the original. Also, Rituximab hasnât been fully characterized, hence the discovery of new uses. There is no such thing as generic when it comes to -mab therapeutics.
Point is, the cost to create Ocrelizumab may be legitimately higher than Rituximab.
Fetal stem cells also apparently can stop degeneration from MS abd regress it (heal the damage) if disease progression hasn't damaged the body's healing mechanisms too much; emcell.com
That was exactly my first thought as well.
Do I want to know how they get mice with severe spinal cord injuries to test on? I'm guessing it's exactly what I think it is, but I'm wondering if there's another way that it happens.
Itâs what you think it is, and it happens to more than just mice. I toured a bioengineering lab where they were actively severing the spines of chimpanzees to perform fiber rerouting experiments. I think the normal citizen never thinks much if at all about this kind of thing because theyâre never exposed to it. A few researchers have opened up to me personally about their personal psychological trauma caused by involvement with animal experimentation. A couple PhD candidates I know changed fields entirely. One to ecology and another to environmental engineering. I personally moved forward with bioinformatics.
Edit: that isnât to say that this result isnât exciting for human welfare. Weâll see if it translatesâŚ
I was originally a biology major and only ended up finishing the minor in part because of this. We had a lab assignment to do a live vivisection of a limpet to be able to view some of the circulatory systems in play in a still-living creature. We were supposed to paralyze them first, but whatever I did was incorrect. That thing was writhing and squirming and trying to get away and showing all the outward physical signs of being in pain the entire time.
Limpets don't even have brains, just cerebral ganglia, so it's likely it isn't really a sentient creature that has any conscious awareness of what is happening to it, but man, that scarred me. It felt like I was torturing something horribly and I knew that was not the career for me. There is no way I'd have ever been able to do that to a mouse.
This is absolutely in the moral gray. The greater good, lesser of two evils, however you want to describe it whether it's right or wrong will get down to your personal beliefs.
I had a family member involved in a cancer research that used mice and although he admitted it was sad, he did call them heroes. Understandably, I don't think that satisfies anyone strongly aligned with animal rights. In many other sciences we've been able to use simulation as a first step, but that is still out of our reach for biological systems.
A hero makes heroic choices. These mice aren't making choices.
Reminds me of "The ones who walk away from Omelas". Clearly not a one-to-one analogy, but close enough to make the connection.
I'm sorry you were downvoted for asking that. I think it's a fair issue to raise. Assuming the mice are intentionally injured to allow testing, it seems reasonable, to me, to question the ethics of that. Of course it's easy to say "they're just mice, who cares?" but it's not wrong to ask "they're living creatures as well, shouldn't we care?" I expect the response to be "it's justified given the benefits we derive for humans, based on this mouse based research", and probably most people would agree with that. But perhaps not everyone would.
Also consider the number of really scary books/movies out there rooted in the idea of "medical utilitarianism." For one example, this issue is addressed in a show called Biohackers that I just started watching. And even in real life, people have tried to justify a lot of really sketchy stuff over the years, in the name of "the greater good".
We do have an alternative to animal testing. We can use humans who are desperate enough to volunteer to a medical experiment knowing that it might not work and could potentially make things worse. The purpose of animal testing in situations like this is to catch early problems before the final human testing. Computer simulation can do a lot to minimize the need for animal testing, but I don't think we are there yet where we can go directly from a simulation to human testing.
I do not however like to view it as medical utilitarianism. The testing will happen regardless if the test subject are human or mice, because people do still want the medical cures. People are however less sad if an experiment accidentally killed a bunch of mice than if a bunch of human test subjects died. Historically people tend to use military service men as test subjects, which is why much of medical knowledge is based on test subjects of a specific gender (male) and age group (20-35). Not that long ago (~1950) people also used people with mental disabilities and orphans. Going just a decade earlier and people used prisoners and war and people deemed unwanted. Hopefully computers will one day replace the need for testing.
> We do have an alternative to animal testing. We can use humans who are desperate enough to volunteer...
This situation would presumably only arise because somebody else previously made the decision not to perform that experiment on an animal, but instead wait until a human suffers enough to become desperate enough to volunteer. That decision resulted in human suffering (albeit in the form of the trolley problem). Was that decision acceptable? How much human suffering, and/or how many humans suffering, is equivalent to one animal? Does sapience make a difference to this calculation?
I'm not saying this makes animal testing OK. My point is just that testing only on human volunteers isn't a magical solution to this ethical problem.
At least with animal subjects, you can ensure that the health, age, and severity of the 'injury' is exactly the same with all subjects.
You'll never get that with humans even if you have plenty of volunteers.
The the answer in the science and medical communities is Almost Never "they're just mice, who cares"
It is rather that this is an important experiment that can't be done any other way and can have large benefit for humans
The the answer in the science and medical communities is Almost Never "they're just mice, who cares"
That's fair. My comment above was maybe overly glib in that sense. But I was just trying to capture the general spirit of the thing, not write an essay, due to limits of time, interest, and knowledge on my part.
It's funny how this cost benefit calculation is considered valid when applied to research on mice, but any such calculation used to try to justify research on humans would give a "divide by 0" error. I think there's an inconsistency there somewhere.
"it can't be done any other way" strikes me as pretty thin. Whereas we may not be able to conceive of another way at this point in time, it does no good to imagine that this condition will continue in perpetuity.
Another good question is whether mice are a good analogue for humans as far as spinal injuries
My brother was researching brain regeneration in rats, and he said they used cryogenically induced lesions as a test bed. So probably something similar.
It is exactly what you think it is.
> The therapy also induces myelin to rebuild around axons and reduces glial scarring, which acts as a physical barrier that prevents the spinal cord from healing
This gives the impression that this would need to be administered before any scaring takes place. It is probably not a remedy for people with old injuries.
This, however, seems to suggest that the therapy actually reduces pre-existing scar tissue:
> the breakthrough therapy dramatically improved severely injured spinal cords in five key ways: (1) The severed extensions of neurons, called axons, regenerated; (2) scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished;
Yeah, but this is incredible if it works at the human level.
My friend was in a car accident and a subwoofer that wasn't tied down ended up striking in him the back paralyzing him from the mid-back down. Years and years of heartache for both my friend, and the other friend who installed the subwoofer without tying it down.
There was a lot of things wrong that allowed this to happen, but knowing future people with injuries like my friend whom this therapy could save or alleviate makes me incredibly excited.
Maybe a dumb question but....
If scar tissue forms after an injury and blocks the area (on both sides of the nerve, I assume), like this ---x x--- . Could you then cut the scarred area away, creating "new" injury that this treatment could cure?
----x x----
---| |---
---**---
I remember reading a story many years ago a about a boy that got a nerve severed and later they opened the wound to remove the scar in the nerve and reconnect the nerve, so it regrows. The problem was that after cutting the scar, the nerve was shorter, so they have to take a shortcut in the elbow.
I can't find the story, but these links have info that is similar enough to be confident my memory is not too bad. http://www.rebeccaayers.co.nz/procedures-and-information/han... https://en.wikipedia.org/wiki/Nerve_allograft
Cool! I am glad that it might be possible and that this might even be able to help those who have old injuries then!
My wife has internal scarring and adhesion(filaments of scar tissues) from appendicitis. This causes complications and her intestines can get twisted instead of moving freely over each other like they normally would. I asked if the adhesion could be cut to allow free movement but unfortunately it's sort of like a hydra, you cut one and it will form more/new adhesions.
I've always wondered... and so far have been unable to Google this: Does the non-nucleus part of a severed nerve cell die? If so, that would mean we only have a small window to "rejoin" severed CNS nerve cells, right? Nerve cells can be very long, I think up to a meter. I'd assume this includes spinal nerve cells of the CNS, which don't regrow. If the cells are severed, like in a spinal injury, that means there's a half-cell fragment with a nucleus, and the other half is the axon that's been cut away without a nucleus. Wouldn't the fragment without a nucleus shrivel up and die? That would be my intuition because I'd assume the nucleus is necessary to keep a cell alive.
Yep. The nerve soma(the cell body) does not die when the nerve is cut. The axon distal to the cut dies. The living axon tries to grow into the 'scaffold' of the axon part that died. This can take months and doesn't always restore full functionality.
I would assume that the entire cell would die without the membrane to hold everything together.
PNS nerve cells regenerate axons: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846285/
so we just have to inject stem cells into the area where there are a lot of damaged nerve cells without nuclei and have these cells fuse with the damaged remnants. Just throw some PEG in there with the stem cells?
I find myself wondering whether a useful testing step between mice and people might be the community of small dogs with IVDD. French bulldogs, dachshunds, and corgis seem particularly susceptible and many of them wind up with rear paralysis. https://www.thedogsdown.com/how-can-ivdd-cause-paralysis/
My wife works on regenerative medicine for spine and they use dogs (and horses) a lot. Cells are similar and they suffer from the same problems. It's mostly dogs who die of natural causes though as dogs are too cute to experiment on...
Youâd like to think that, but weâve had multiple beagle rescues who would disagree. And they were the control population because the actual test subjects get killed.
It's not unusual for dogs to be used in medical research. Aside from the more well-known use of rats, rabbits are also commonly used.
The last section about generalizing the treatment is a bit underwhelming. Have they seen any evidence it can be used outside this sort of repair? What about for neuropathies, as from diabetes or surgeries? Stroke? Other dysfunctions (e.g. erectile/genital) having nervous system issues as a contributing factor?
Any treatment "might" have more general applicability--but surely there is some specific direction/class of these conditions that are indicated to be more appropriate to apply the treatment to than others. I wish they'd gone in more depth here.
A lot of cells will only grow when they feel familiar surroundings. This gel technique is used with various cell types. For example, pancreas cells will not grow alone in glass, but they will grow inside a specially-made gel that mimics their expected extra-cellular matrix [0].
[0] "A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids" https://doi.org/10.1038/s41563-021-01085-1
IN MICE.
Seriously, mice are really really good at healing these injuries. You can find dozens of 'heals spinal cord injuries IN MICE' articles.
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