Hi everyone, hoping to find someone smarter than me. I do lots of searching about the discovery of new non toxic demethylating drugs and CRISPR techniques. Just wondering if any of this is applicable to the brain as there is a lack of cell division. I just get my hopes up about it as I can’t find enough resources on it or maybe I’m not looking in the right place. I used to come here a lot when I was helpless so I’ll try once more. I know there’s lots of smart people here that used to give me hope.
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Currently, there’s a lot to look forward to. I’m not fully educated on the science side of things (its never been my strong suit), but we’ve got the Kiel study starting this year. I personally have been reaching out to epigenetics researchers in my state, in hopes to get this issue on their radar. I encourage you to do the same!
I’d like to know about the brain targets and cell division issue as well when you get time
Borax did mention once that this can possibly all be reversed by targeting the androgen receptor dysfunction
So if you correct that then all the gene silencing can potentially get undone since it might be downstream
Is it possible to edit the methylation state of neurons?
This is a study done on mice that was published in September of last year. The tldr is they used dCas9 to increase methylation of the amyloid precursor protein in mice models of Alzheimer’s both in vivo and in vitro. The idea was that if they methylated the amyloid precursor protein (which they speculated was at least partially responsible for the clinical symptoms of Alzheimer’s), they could improve Alzheimer’s symptoms.The results:
The cultured APP-KI mouse primary neurons exhibited an altered DNA-methylation pattern on the APP promoter after dCas9-Dnmt3a treatment. Likewise, the APP mRNA level was significantly reduced in the dCas9-Dnmt3a-treated wild-type and APP-KI mouse primary neurons. We also observed decreased amyloid-beta (Aβ) peptide level and Aβ42/40 ratio in the dCas9-Dnmt3a-treated APP-KI mouse neurons compared to the control APP-KI mouse neurons
the in vivo methylation of APP in the brain via dCas9-Dnmt3a treatment altered Aβ plaques and attenuated cognitive and behavioral impairments in the APP-KI mouse model.
While this is a mouse study, there does appear to be significant interest, funding, etc. in researching and developing tools that will enable the manipulation of gene expression in the brain since it looks so promising. So hypothetically, if for whatever reason, correcting the genetic causes of this disease didn’t rectify the epigenetic catastrophe, the tools to repair that should come along soon too.
What about x,y,z issue associated with neuronal editing?
There’s also a number of issues associated with using CRISPR in clinical practice outside of the one that you mentioned but there are lots of smart people and lots of money behind solving those problems.
Take this paper for example:
https://www.sciencedirect.com/science/article/abs/pii/S0142961222005993
It talks about some of the (very long list of) challenges associated with using CRISPR for in vivo editing in neurons - then talks about the solutions that have been developed to address them - as well as presenting their solution to yet another problem that’s been consistently brought up in literature.
Will the tech be capable of solving this disease?
I think this is the question that most people are really asking whenever they’re posting x,y,z concern about CRISPR.
Here’s an article talking about how CRISPR trials to treat diseases in humans have been going. And the key takeaway is that most of the results look promising, and there’s a lot of interest in working on solving the problems with the ones that don’t. I would say you shouldn’t worry about the technology and whether it’s going to work. And I say this because as I mentioned earlier - there is a lot of incentive, a lot of money, a lot of smart people, and the output that’s been observed so far has been - a lot of progress.
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