[HN Gopher] A new twist on using 'personalized' stem cells for s...
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A new twist on using 'personalized' stem cells for studying
dementia
Author : elorant
Score : 66 points
Date : 2021-04-14 18:43 UTC (4 hours ago)
(HTM) web link (singularityhub.com)
(TXT) w3m dump (singularityhub.com)
| mjfl wrote:
| As someone who does research in biology and therapeutics, it
| seems to me that Alzheimer's research is such a dismal field. We
| don't have a good idea of what causes it, not only do we not have
| good animal models, we have _misleading_ animal models which
| reflect some of the traits of Alzheimer 's but nothing translates
| to humans. There was this mouse model they made which developed
| these plaques like in Alzheimers and they found they could clear
| them with brain stimulation pretty well - but trying it in humans
| there was no effect.
| freewilly1040 wrote:
| > There was this mouse model they made which developed these
| plaques like in Alzheimers and they found they could clear them
| with brain stimulation pretty well - but trying it in humans
| there was no effect.
|
| Rinse and repeat many times over, I think. This dynamic is what
| pushed me away from the field in general, the knowledge that I
| could spend my whole career working on a mouse model that
| there's reason for only tepid confidence in.
| bumby wrote:
| There's a Twitter feed dedicated to this caveat
|
| https://mobile.twitter.com/justsaysinmice?lang=en
| misterkrabs wrote:
| Is there a paper on that? I'm so interested.
| inglor_cz wrote:
| Do you think that the "organ on a chip" method could help?
|
| Having tiny human brains (or brainlets) would be a closer model
| than using any animal, or not?
| amelius wrote:
| > Do you think that the "organ on a chip" method could help?
|
| Can we even reliably diagnose Alzheimer's based on brain
| tissue alone? If so, what do we look for?
| bumby wrote:
| I think tau protein is a correlate?
|
| As far as I know, it can only be tested post-mortem but
| there is some research related to detecting it with blood
| tests.
| mjfl wrote:
| Missing a lot of signals from the in vivo context - for
| example taking a naive approach to organoids typically means
| you're going to be missing vascularization, which is
| essential for the architecture of the brain in vivo.
|
| Also typically organoids present as very immature brains,
| whereas Alzheimer's patients sort of have "maximally mature"
| brains.
| f6v wrote:
| I'm not an expert, but suppose Alzheimer's onset and
| progression is affected by the gut-brain axis. There's no way
| for an organoid to capture that.
| amelius wrote:
| Yes, also hormones controlling e.g. sleep, which is
| essential for brain function.
| The_rationalist wrote:
| Unrelated: Tifasopam has been shown to have groundbreaking
| efficacy on reverting cognitive impairment:
| https://pubmed.ncbi.nlm.nih.gov/31981560/
|
| btw I believe that Tifasopam is the best long term anxyolitic
| medication out there: No tolerance No cognitive impairment No
| sedation No side effects Very potent
| paulpauper wrote:
| The problem with AD is by the time the symptoms appear, the brain
| is already irreparable ravaged. The damage is actually
| macroscopically visible. Treatment would have to begin long
| before symptoms show, which would mean identifying people who are
| at risk.
| kgin wrote:
| I think any person newly diagnosed with alzheimers would jump
| at the chance to stop its progression.
| JamesBarney wrote:
| Once you get an alzheimer's diagnosis your brain is pretty
| ravaged. The diseases process probably starts decades before
| most diagnoses.
| prepend wrote:
| And I think anyone newly diagnosed would love to have
| progression stopped at diagnosis.
|
| What's your point?
|
| It's not a total cure and restoration, but it's better than
| now- where your brain is ravaged at diagnosis and gets
| worse until death.
| max-ibel wrote:
| If you have MRI scans of your brain, you can upload them to
| brainkey.ai to track differences over time. They even offer a
| [?]400USD MRI scan out of pocket if you live close to one of
| their participating scanning centers (e.g. in the Bay Area).
| btilly wrote:
| Luckily https://www.nia.nih.gov/news/blood-tests-show-promise-
| early-... points at a test that looks like it can figure out
| who will develop Alzheimer's years before there are any
| symptoms. (In their dataset, up to 20 years before.)
| [deleted]
| gervwyk wrote:
| There is a fascinating episode on Alzheimer treatment using some
| sort of frequency exposure [0], I don't know much about this but
| radiolab made me really excited that there could be an end to
| Alzheimers one day soon. Studies like this and the hopeful
| potential benefits unlocked with crispr also!
|
| https://www.wnycstudios.org/podcasts/radiolab/articles/bring...
| halfmatthalfcat wrote:
| _Crush_ Alzheimer's.
| timy2shoes wrote:
| I think the overall goal assumes that genetics causes
| Alzheimer's, which is (in my opinion) a questionable assumption.
| That's not to say that the production of model systems for
| Alzheimer's will be useful, but will it be worth the tens or
| hundreds of millions of dollars that this will cost? -\\_(tsu)_/-
| kgin wrote:
| Gene therapy can treat diseases that aren't specifically caused
| by genetics.
| timy2shoes wrote:
| Yes, but that would require knowing how to rescue the
| phenotype, in this case healthy neurons and connections.
| Alzheimer's is not like Parkinson's, which you can (most
| likely, see the recent work from BlueRock) treat by replacing
| dopaminergic neurons or rescuing the dopamine production.
| WalterBright wrote:
| The book "The End of Alzheimers" makes a case that there are 36
| causes of Alzheimers. It's the combination of those causes that
| results in the disease. The more of those causes a person has,
| the more likely they'll develop Alzheimers.
|
| This is why research and treatments that focus on only one
| cause have all been stymied and went nowhere.
|
| The book's treatment program is to address as many of the
| causes as possible.
| MetaWhirledPeas wrote:
| As long as it's not diverting funds from anything more
| promising then spend all the money you want I say. Try
| everything. You may fail more often but you'll find the right
| answer faster.
| timy2shoes wrote:
| With a limited NIH budget this will necessarily divert funds
| from other endeavors. In addition, I think such programs
| entrench the large lab bias prevalent in academia right now.
| benrapscallion wrote:
| There's a remarkable amount of hyperbole in this article (but not
| the original publication). In plain language, this is a project
| to generate, characterize, and openly share the data for iPSC
| models (and presumably neurons from them) bearing 100 APOE
| disease-associated mutations.
|
| It must be remembered that one reason many AD drugs have failed
| is because models don't capture the disease accurately and that
| may well turn out to be the case here.
| kick_in_the_doo wrote:
| Do AD drugs attempt to reduce the concentration of APOE in the
| brain? If so, is it known if these drugs either failed to
| reduce the concentration of APOE, or succeeded in reducing
| concentration but still didn't work?
| benrapscallion wrote:
| "Reduce APOE" is an oversimplified view. The mechanisms by
| which the AD-associated E4 genotype (arg112, arg158) results
| in disease are still poorly understood. The main therapeutic
| hypothesis for AD is to reduce the levels of pathogenic
| plaques and aggregates using antibodies.
| kick_in_the_doo wrote:
| Interesting. And these studies have shown that medicine
| which reduces these plaques doesn't actually help with AD
| symptoms?
| dang wrote:
| I've pinched the title from https://www.ninds.nih.gov/News-
| Events/News-and-Press-Release..., which the OP points to, since
| it seems less hyperbolic and more precise.
|
| Not sure if the article itself should be changed also...
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