As you know we have been trying to work out how my “favourite drug” works. Over the years it has had more proposed mechanisms than I have had restaurant meals (this year). We have a new one here and it has a direct action on Th17 cells. This is done by the real McCoy and the Я тоже alternative. That is a Russian “Me-Too” copycat drug
Glatiramer acetate (GA) is approved for the treatment of multiple sclerosis (MS). However, the mechanism of action of GA in MS is still unclear. In particular, it is not known whether GA can modulate the pro-inflammatory Th17-type immune response in MS. We investigated the effects of original GA (Copaxone®, Teva, Israel) and generic GA (Timexone®, Biocad, Russia) on Th17- and Th1-type cytokine production in vitro in 25 patients with relapsing-remitting MS and 25 healthy subjects. Both original and generic GA at concentrations 50-200 μg/ml dose-dependently inhibited interleukin-17 and interferon-γ production by anti-CD3/anti-CD28-activated peripheral blood mononuclear cells from MS patients and healthy subjects. This effect of GA was reproduced using purified CD4+ T cells, suggesting that GA can directly modulate the functions of Th17 and Th1 cells. At high concentrations (100-200 μg/ml), GA also suppressed the production of Th17-differentiation cytokines (interleukin-1β and interleukin-6) by lipopolysaccharide (LPS)-activated dendritic cells (DCs). These GA/LPS-treated DCs induced lower interleukin-17 and interferon-γ production by autologous CD4+ T cells compared to LPS-treated DCs. These data suggest that GA can inhibit Th17-immune response and that this inhibitory effect is preferentially exercised by direct influence of GA on T cells. We also demonstrate a comparable ability of original and generic GA to modulate pro-inflammatory cytokine production.
This study says we dont know how glatiramer acetate works. It was made with the belief that it had something to do with it being related to myelin basic protein and the formation of regulatory Th2 (Interleukin 4 ) secretion. This study, if correct, says that is a load of cahones as it is active when there is no myelin basic protein/peptide in the system and no Th2 in the system.
It inhibits T cell responses at 200 microgramme (thousandth of a gramme) for gamma interferon and interleukin 17. We say “wow” mechanism sorted. However, whilst it may give a great response for some, it doesn’t seem to work for everyone. So we have to think about that but the other thing we have to think about is dose in humans.
Glatiramer is injected at 20mg a day in some formulation and it goes under the skin. So if it all got into the blood, it would give a concentration of 4microgramme per millilitre (thousandeth of a litre). However it has been measured and it has been reported that the concentration in the blood is maximum plasma concentration of 69 to 605 ng/mL. So in the above graphs at that does it would do nothing.
Maybe keep looking for a new mechanism……Maybe start by not looking at T cells. Let’s all shout its behind you as you wont find the answer if you look in the wrong place
@Mouse Doctor do you mean they should look at B cells?
One possibilitity…but it has been done
I read your message about GA and I’m pretty sure you’re screaming “old school “ with teeth clenched.
The statement it works for some is how I feel. It works for me, I think. I take every single expensive welt raising shot leaving ugly indurated bumps. I figured it works because 1. It’s So Expensive. 2. My Dear old Dr. Panitch told me it works. Protein Soup. I thought the mechanism of action is a decoy for the anti myelin creatures. Chomp chomp. Pac-Man like. I also wonder on studies if patients Really take all the doses. I told my Dr. when I was on CombiRx study if I’d known the Interferon was the placebo I wouldn’t have taken it. I wouldn’t have told them. Studies have their trials too 😎
Happy it works for you. The bumps are possibly related to atrophy of fat,
It works because it is expensive….Em
Decoy for myelin….It is hard to think how it does some many things. It has to be more than myelin…It inhibits autoimmune retinal disease but there is no myelin in the eye
Probably the dumbest MoA ever for GA… proteasome false substrate? Did anybody propose it? It gets in the pocket and competes with other stuff for digestion without being digested in relevant manner? If I remember correctly GA is a peptides mix or sort of it… it could get to the proteasome and mess up just a bit with it.
If NGD shows benefit of proteosome inhibitors…watch this space
I am watching… (only watching 🙁 )
I found this and it seems to say something.about GA and proteasome and MBP but it may tell something else
https://www.hindawi.com/journals/bmri/2014/926394/