Oh I forgot to mention (but this goes without saying) I take 6mg rapamycin every Monday 
***standard small print - nothing I post in this forum or elsewhere is intended to be taken as medical advice. I am not a trained medical practitioner!!!
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Neo
#9
Will look into some of these links - thanks.
It seems that the two protocols you refer to above are about clearing senescence more than they are about general autophagy - how do you think about those two concepts while overlapping in someways not being the same thing? Seems that was is needed for MS is more the autophagy part?
Good point. True, I suppose not all dysfunctional cells are senescent. My protocols seems to target the latter (senescent cells) as a subset of the former (dysfunctional cells), whereas autophagy (targeting any dysfunctional cell) is the larger concept (which includes senescence clearance, given that a senescent cell is dysfunctional). Have I understood that correctly?
I need to look into autophagy proper, I have just been going with D&Q, Fisetin, Treehelose and Spermidine as doing both, but you’re right - I’m not sure that it clears dysfunctional cells that are not senescent.
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Neo
#11
Think that may be directionally correct, but I’m not that well read up on this.
(May be more corner cases, but fwiiw, also think there may also be cases of senescent/zombie cells that “normal” autophagy may fail to clear but that senolytic therapy can clear)
I posted about autophagy inducers in neurodegenerative diseases in the mTORC1 (but not mTOR2) inhibition post.
I’ve uploaded the paper here too:
PIIS0021925819405528.pdf (577.9 KB)
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Neo
#13
Cross linking to this as it relates to this topic
JuanDaw
#14
Beginning from day 7 post immunization (d.p.i.), animals received an i.p. injection of saline, DM 0.1 mg/kg (DM-0.1) or DM 10 mg/kg (DM-10) (Sigma) once daily.
Overall, our results reveal a novel protective effect of low dose DM dextrometorphan) in autoimmune CNS inflammation, and demonstrate that a possible mechanism of action is via inhibition of NADPH oxidase and decrease of CNS leukocytes infiltration. These exciting findings may provide useful information leading to a new, inexpensive strategy for treating MS.
.1 divided by 12.3 times 70 (70 kilo human) is about a half mg a day. The adult dose for cough is 20 mg four times daily. So that is one fortieth of the cough dose, taken once a day. Cough dose is taken four times a day. Dextrometorphan plain (no expectorant like guaifenesin) is available over the counter (CVS, Walgreens). The dose may need to be increased, to match the DM in the mice’s system, after injection. But even at 2 mg per day, Dextrometorphan still has effects on NADPH oxidase, which seems to be the mechanism of action.
There is also a DM formulation with low dose quinidine.
Avanir Pharmaceuticals has been conducting trials of AVP-923 in its current and related formulations for several years as a treatment for pseudobulbar affect in a number of disorders, including MS, ALS, Alzheimer’s disease and stroke. AVP-923 is a patented, orally-administered combination of dextromethorphan and an enzyme inhibitor known as quinidine; quinidine is a drug that inhibits the metabolism of dextromethorphan which results in a sustained elevation of dextromethorphan in the brain.
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Neo
#15
People have any thoughts on this?
Cheap, generic medicine for allergy helps repair in MS in one trial, other trial stopped
To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage.
Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported.
in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible.
receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for*** 60 days (group 2)***.
> Clemastine is an antihistamine used to relieve symptoms of allergy, hay fever, and the common cold
Both over-the-counter product and available via prescription in the US at least
But:
Clemastine Arm of TRAP-MS Trial Halted Following Increased Disability Accumulation in Progressive Multiple Sclerosis
See also follow up deeper analysis of the original trial
https://www.pnas.org/doi/10.1073/pnas.2217635120
Its generic and cheap
https://www.goodrx.com/clemastine
Dosing in first trial is higher than uses for allergy: https://reference.medscape.com/drug/clemastine-343388
Yeah, muscarinic antagonists (clemastine has some off target muscarinic antagonism) have been shown to increase remyelination in vitro. The fact that the progressive patients saw a worsening might be due to clemastine’s other cholinergic off target effects (from memory only the M3 appears important in remyelination, but clemastine also affects M1 & M2) and progressive patients tend to have less cognitive reserve to compensate for cholinergic effects.
Interesting that above dextromethorphan was mentioned. It’s a known NMDA receptor antagonist. Know what is prescribed off label for MS-associated fatigue? Amantadine, another NMDAr antagonist (though it’s also a dopaminergic agent. It works very well for fatigue, btw)
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Neo
#17
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AnUser
#18
Yes Rhonda Patrick, we know exercise is healthy. It’s groundhog day for like 7 years.
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Neo
#19
@AnUser did you know it helps with myelin sheet growth - I don’t think most people were aware of that…
That is a massive issue in several big diseases like MS (and aging) - and while big biotech investments have gone into it no one has cracked it via any medicine or therapeutic yet
So for people on this specific thread this might be very interesting because of the specific focus of her tweet and the study , not because of that exercise is generally goo
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AnUser
#20
I don’t think it does so it does not inform me on whether to exercise or not (and I think the same would be true for MS patients), lots of good reasons to exercise either way.
Neo
#21
How come?
The paper is in a good journal, research by a very credible team and based on MRI imaging data that tends to be unbiased…
Adding @adssx as this is relevant for Parkinson’s and other neuro
Evidence of association between higher cardiorespiratory fitness and higher cerebral myelination in aging
Mary E Faulkner et al. Proc Natl Acad Sci U S A.2024.
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AnUser
#22
Mechanistic association study.
Neo
#23
That might mean that it makes sense to say - hey we need more info to say that we know that there is a causal relationship
But you said something fundamentally different:
I don’t think it does
That should require some efficient in the other direction?
Otherwise should it not be I “don’t know” or something more like that?
AnUser
#24
Nah, the null hypothesis is that there is no relationship.
Bicep
#25
This might be a good time to put this up:
Since it is the time of year to harvest aronia berries. Most supplements supply between 50 and 300 mg of ursolic acid. A shot glass of aronia juice supplies that and much more. It remyelinates the nerve sheaths. Must not work very well, but that’s the hype.
Unfortunately we can’t get anybody to come and mechanically harvest the 2 acres of aronia we have, so have been just picking them by hand for ourselves. It’s a terrible waste, but such is the state of organic farming. A different set of problems from those of the factory farm for sure. People don’t want to pay.
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DrT
#26
Rosemary is also rich in ursolic acid.
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@Walter_Brown maybe you stated this elsewhere but how would you compare DAV protocol vs dasatinb and quercetin?
Anyone else that has done both, please chime in too.
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