Aa
Could microglia eradication provide relieve for this hell?
There's this new drug currently in phase 1b or 2
It's called plx3379
It destroys the IFN induced chronic activity of the microglia, by killing the microglia itself.
After a week of cessation of treatment the microglia grew newly and insensitive.
Couldn't that provide a solution to this HELL post IFN?
Ah, the stuff has side effects but they gave it to end stage tumor patients for about 250 days in doses of 1000mg / d
I suggest that some weeks taking this stuff could substantially improve brain functioning, by "resetting" the microglia
It's called plx3379
It destroys the IFN induced chronic activity of the microglia, by killing the microglia itself.
After a week of cessation of treatment the microglia grew newly and insensitive.
Couldn't that provide a solution to this HELL post IFN?
Ah, the stuff has side effects but they gave it to end stage tumor patients for about 250 days in doses of 1000mg / d
I suggest that some weeks taking this stuff could substantially improve brain functioning, by "resetting" the microglia
Plus, the stuff is really expensive ( 400$ for 1000mg, but I think I order it and do a self test). 20g should do the trick.
Outcome 1:I'm good as new
Outcome 2:i continue to deteriorate
Outcome 3:I improve
Outcome 1:I'm good as new
Outcome 2:i continue to deteriorate
Outcome 3:I improve
Well, I got a semi ok for ordering the chemical. I will do it for 20 days 1000mg/d
And the sides are manageable, being fatigue the most common. Most severe but only after several months grade 3plus adverse events are neutropenia, andvonebi forgot. But that only occured in a dose escalation study after numerous cycles
They gave it to mice at 290mg/kg, after 21 days >95% microglia was eradicated. After 21 days recovery microglia repopulated to normal amounts in normal shapes and sizes.
Is there somewhere I can go to research this drug further.? It sounds very
promising.
https://www.mind.uci.edu/wp-content/uploads/2014/09/Green.pdf
http://faculty.sites.uci.edu/kimgreen/files/2011/03/9977.full_.pdf
not easy to read/understand the details(NeuN, IBA1 markers for example) but the principle should be clear. cutting an old, ill tree to let it grew newly
http://faculty.sites.uci.edu/kimgreen/files/2011/03/9977.full_.pdf
not easy to read/understand the details(NeuN, IBA1 markers for example) but the principle should be clear. cutting an old, ill tree to let it grew newly
though im at the beginning of this project. following questions have to be solved first:
how much,
how long,
how expensive,
side effects
how much,
how long,
how expensive,
side effects
thank you.
MRI has changed science dramatically.
When I have the time I will look up one revolutionary finding that was posted on the LDN forum due to MRI.
MRI has changed science dramatically.
When I have the time I will look up one revolutionary finding that was posted on the LDN forum due to MRI.
i realized something today.
Imagine 'primed' microglia within the CNS. Activated by multiple factors.
The agent inhibits CSFR1 which leads to apoptosis (cell death) of microglia.
A complete wipeout isn't necessary. (and would maybe too toxic because of the daily amount needed)
Mice receiving 16-75mg/kg were depleted of microglia but in the same time, new repopulated.
Imagine the 'sick' microglia. If one is doing a regimen of maybe 1000mg/day for 3 or 4 months every unique microglia is replaced by a new one. It will kill all the sick microglia sooner or later. the amount of present microglia is not drastically reduced, it just replaces them bit by bit...
Imagine 'primed' microglia within the CNS. Activated by multiple factors.
The agent inhibits CSFR1 which leads to apoptosis (cell death) of microglia.
A complete wipeout isn't necessary. (and would maybe too toxic because of the daily amount needed)
Mice receiving 16-75mg/kg were depleted of microglia but in the same time, new repopulated.
Imagine the 'sick' microglia. If one is doing a regimen of maybe 1000mg/day for 3 or 4 months every unique microglia is replaced by a new one. It will kill all the sick microglia sooner or later. the amount of present microglia is not drastically reduced, it just replaces them bit by bit...
Good luck with your experiment
Best if you have your own MRI machine to examine the progress!
Here is the new findings I was looking for:
http://neurosciencenews.com/lymphatic-system-brain-neurobiology-2080/ = Researchers Find Missing Link Between the Brain and Immune System
Best if you have your own MRI machine to examine the progress!
Here is the new findings I was looking for:
http://neurosciencenews.com/lymphatic-system-brain-neurobiology-2080/ = Researchers Find Missing Link Between the Brain and Immune System
I find the language of science hard to understand but these findings make
complete sense and can see that they will lead to more effective
medicines for a wide range of neurological complaints. My subjective experience is that interferon caused inflammation in my brain and from that
all the side effects flowed. Given this research this seems an accurate supposition.
complete sense and can see that they will lead to more effective
medicines for a wide range of neurological complaints. My subjective experience is that interferon caused inflammation in my brain and from that
all the side effects flowed. Given this research this seems an accurate supposition.
i contacted Dr Green from the Green Lab who's writing about this method.
Yes, the language is hard and one has to research things to understand the logic.
thank god my father has a PhD in Chemistry and teached me about chemicals and basic pharmacology from a young age on.
I struggled with the markers, IBA1, GFAP, S100 and so on but it*s easy to understand. one hasn't to fully understand every detail, it's sufficient to realize that there is no collateral damage like with Diphteria Toxin, that would be too unselective. it is sufficient to realize that the agent does not kill other cells than microglia within the CNS. otherwise i would stay the hell away from this experiment. the inhibitor is highly selective, Interferon is just the complete opposite.
Yes, the language is hard and one has to research things to understand the logic.
thank god my father has a PhD in Chemistry and teached me about chemicals and basic pharmacology from a young age on.
I struggled with the markers, IBA1, GFAP, S100 and so on but it*s easy to understand. one hasn't to fully understand every detail, it's sufficient to realize that there is no collateral damage like with Diphteria Toxin, that would be too unselective. it is sufficient to realize that the agent does not kill other cells than microglia within the CNS. otherwise i would stay the hell away from this experiment. the inhibitor is highly selective, Interferon is just the complete opposite.
and yes Bruin, IFN causes brain inflammation. Memory impairments, cognitive impairments, psychomotor degeneration, fatigue... that all comes from the inflamed brain. hang in, i will do this experiment and i will do it for everyone with this problem, regardless of the outcome.
Thank you very much for explanations.....hope that it is not too much
of an experiment and that you get a great result. Do you have a start date ?
of an experiment and that you get a great result. Do you have a start date ?
ok. weird mode. i have to vent.
thanks, what TEMPORARY helps with memory, cognitive issues are stimulants like MPH, Amphetamine based Antidepressants, stimulants though one has to be very careful to not overdo them and upregulate inflammation as a side effect. I take ALA to deal with the free radicals that the microglia spits out, but i'm often too weak to think about it, remember it and so on. I get Bupropion at the highest dose available (300mg) but i struggle with it somehow... i got some MPH an hour ago and did about 80mg (40 unret. 40 ret.) to get some energy to clean up my bedroom cause my mum plans to get here tomorrow.
it's always a give and get... get energy, loose memory... my psych drugs should get changed... since the LDN reduced inflammation, stimulant drugs seem to flare it up in a way and crashes are programmed... i*m much more weird on stimulants than without... my doc is in it*s holiday and their assistant didn't want to change anything on the Antidepressive medication.
i plan to step down a bit and get on Amitriptyline, it*s an Antidepressant and reduces inflammation as a side effect.
The project will start as soon as i am on a stable regimen and not think and act like a computer with a virus (like today), i gues i start in about 6-8 weeks.
thanks, what TEMPORARY helps with memory, cognitive issues are stimulants like MPH, Amphetamine based Antidepressants, stimulants though one has to be very careful to not overdo them and upregulate inflammation as a side effect. I take ALA to deal with the free radicals that the microglia spits out, but i'm often too weak to think about it, remember it and so on. I get Bupropion at the highest dose available (300mg) but i struggle with it somehow... i got some MPH an hour ago and did about 80mg (40 unret. 40 ret.) to get some energy to clean up my bedroom cause my mum plans to get here tomorrow.
it's always a give and get... get energy, loose memory... my psych drugs should get changed... since the LDN reduced inflammation, stimulant drugs seem to flare it up in a way and crashes are programmed... i*m much more weird on stimulants than without... my doc is in it*s holiday and their assistant didn't want to change anything on the Antidepressive medication.
i plan to step down a bit and get on Amitriptyline, it*s an Antidepressant and reduces inflammation as a side effect.
The project will start as soon as i am on a stable regimen and not think and act like a computer with a virus (like today), i gues i start in about 6-8 weeks.
Venting is certainly very healthy!
I hope to NEVER be on ADs again but what you have researched is certainly interesting!
Amitriptyline is on on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system (according to Wikipedia).
LDN does change everything agreed!
I hope to NEVER be on ADs again but what you have researched is certainly interesting!
Amitriptyline is on on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system (according to Wikipedia).
LDN does change everything agreed!
since TLR4 has to be inhibited (that's what LDN does) :
Eight tricyclics were tested for effects on TLR4 signaling in HEK293 cells over-expressing human TLR4. Six exhibited mild (desipramine), moderate (mianserin, cyclobenzaprine, imiprimine, ketotifen) or strong (amitriptyline) TLR4 inhibition, and no TLR4 activation. In contrast, carbamazepine and oxcarbazepine exhibited mild and strong TLR4 activation, respectively, and no TLR4 inhibition. Amitriptyline but not carbamazepine also significantly inhibited TLR2 signaling in a comparable cell line. Live imaging of TLR4 activation in RAW264.7 cells and TLR4-dependent interleukin-1 release from BV-2 microglia revealed that amitriptyline blocked TLR4 signaling
Eight tricyclics were tested for effects on TLR4 signaling in HEK293 cells over-expressing human TLR4. Six exhibited mild (desipramine), moderate (mianserin, cyclobenzaprine, imiprimine, ketotifen) or strong (amitriptyline) TLR4 inhibition, and no TLR4 activation. In contrast, carbamazepine and oxcarbazepine exhibited mild and strong TLR4 activation, respectively, and no TLR4 inhibition. Amitriptyline but not carbamazepine also significantly inhibited TLR2 signaling in a comparable cell line. Live imaging of TLR4 activation in RAW264.7 cells and TLR4-dependent interleukin-1 release from BV-2 microglia revealed that amitriptyline blocked TLR4 signaling
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