ok three time is the charm so here we go with the third post of the evening (now i can cross them out on my to do list)
i went to see Grizzly Bear sunday night and....no wait...i can't post about this just so i can cross it off somewhere. Yeah this is not that type of thing. well neither was the picture posting i guess.
well ok. i come back later.
over all it was good though.
Tuesday, February 6, 2007
that whole MS thing
This is the sequel post to what i was talking about a while ago about MS. Sicne the presentation is over and i am less inspired at the moment and i have other things to do, I will only briefly go into the details of MS vacciantion.
Basically, the IL-17 story boiled down to this: Inject patient with IL-17 and adjuvant, cause immune tolerance to IL-17 to break. Get antibody production. The antibodies neutralize IL-17. Mouse models show a delay in onset of disease and milder symptoms. Not very convincing as far as i am cocnerned because the animals still ended up with EAE and the study was short term. As my prof pointed out, had they continued the study, by day 90, all the mice would've been in the same mess. I guess although I appreciate that IL-17 therapy may be a better target than other interleukin vaccines because of its early inflamatory and downstream role (I.e. its function is not as broad as oh say IL-2, and so its inhibition may have fewere side effects), I still think the same questions of safety (whether it be infection/cancer risk or some other physiological issue) and efficacy still apply here. So i guess in hindsight, I am not too impressed.
Other proposed vaccine strategies:
TCR vaccination. Brilliant idea. Pretty damn safe. will it work? dunno. Basically, this stategy involves priming and activating Th2 (or not) suppressor cells to suppress cells which harbor TCRs that recognize self antigens (I.e. autoimmune Th1 cells). The idea is that Th2 cells recognize peptide sequence of Th1 TCR and suppress it. I think this is a great idea and there is no risk of activating the "wrong" response. But for this approach to work, you pretty much have to genotype every patient individually to figure out what their self-TCR peptide sequence is. I mean they say 90% of patients have these specific sequences but i dunno, the fact that the efficay isn't great tells me something is up. And what i don't udenrstand is where is the APC help coming from? I mean the Th2 cells need APC help no? And there is things there about HLA and MHCI or II or i dunno. basically genetic stuff that i am not too familiar with. Again, this strategy is a good idea but since i don't know enough about many of the details i'll leave things here.
Altered Peptide Ligand (APL) strategy:
what were they thinking?!??! This is a super risky strategy. Inject the patient with a peptide that resembles the self antigen but has a lower binding??!?! this is scary stuff! I am not surprise they observed adverse effects in the clinical trials. Again though, I didn't read much about this so no further comment. Just that I think this is dangerous stuff. I wonder if this is the same story that i heard about a few years ago where things went terribly wrong in the clinical trials of them MS patients...
Ok Copaxone:
it has passed all phases of clinical trials. 8 year long term study (as far as i know the longest existing trial on MS vaccines) and still all is well. according to the discovering scientist 100000 doses are being administered daily.
The way it works is that they this compound (Aka glutatimer(?) acetate (GA) or Cop 1) works by binding to the TCR /MCH receptors really really really strongly. This strong binding out competes binding of the natural self-ligand and apparently more importantly kick starts the suppressive response because of its high affinity. I have no objections against it. The clinical trials speak for themselves.
There are a couple of other strategies as well. Like using bacterial toxins to boost the immune response etc. but since i don't know much about them, i won't go into the details.
anyway, that was that for MS vaccination. Over all i think prophylactic or therapeutic vaccination against autoimmune diseases are perfectly valid strategies. But i guess if we want to dive into immune modulation as a therapeutic method, first we have to learn a lot more about the immune system as a whole and its complex communication web (with itself and other organs/tissues). But that is exactly what we are doing...so...fight the power you immunologists.
one day my friends...one day.
Basically, the IL-17 story boiled down to this: Inject patient with IL-17 and adjuvant, cause immune tolerance to IL-17 to break. Get antibody production. The antibodies neutralize IL-17. Mouse models show a delay in onset of disease and milder symptoms. Not very convincing as far as i am cocnerned because the animals still ended up with EAE and the study was short term. As my prof pointed out, had they continued the study, by day 90, all the mice would've been in the same mess. I guess although I appreciate that IL-17 therapy may be a better target than other interleukin vaccines because of its early inflamatory and downstream role (I.e. its function is not as broad as oh say IL-2, and so its inhibition may have fewere side effects), I still think the same questions of safety (whether it be infection/cancer risk or some other physiological issue) and efficacy still apply here. So i guess in hindsight, I am not too impressed.
Other proposed vaccine strategies:
TCR vaccination. Brilliant idea. Pretty damn safe. will it work? dunno. Basically, this stategy involves priming and activating Th2 (or not) suppressor cells to suppress cells which harbor TCRs that recognize self antigens (I.e. autoimmune Th1 cells). The idea is that Th2 cells recognize peptide sequence of Th1 TCR and suppress it. I think this is a great idea and there is no risk of activating the "wrong" response. But for this approach to work, you pretty much have to genotype every patient individually to figure out what their self-TCR peptide sequence is. I mean they say 90% of patients have these specific sequences but i dunno, the fact that the efficay isn't great tells me something is up. And what i don't udenrstand is where is the APC help coming from? I mean the Th2 cells need APC help no? And there is things there about HLA and MHCI or II or i dunno. basically genetic stuff that i am not too familiar with. Again, this strategy is a good idea but since i don't know enough about many of the details i'll leave things here.
Altered Peptide Ligand (APL) strategy:
what were they thinking?!??! This is a super risky strategy. Inject the patient with a peptide that resembles the self antigen but has a lower binding??!?! this is scary stuff! I am not surprise they observed adverse effects in the clinical trials. Again though, I didn't read much about this so no further comment. Just that I think this is dangerous stuff. I wonder if this is the same story that i heard about a few years ago where things went terribly wrong in the clinical trials of them MS patients...
Ok Copaxone:
it has passed all phases of clinical trials. 8 year long term study (as far as i know the longest existing trial on MS vaccines) and still all is well. according to the discovering scientist 100000 doses are being administered daily.
The way it works is that they this compound (Aka glutatimer(?) acetate (GA) or Cop 1) works by binding to the TCR /MCH receptors really really really strongly. This strong binding out competes binding of the natural self-ligand and apparently more importantly kick starts the suppressive response because of its high affinity. I have no objections against it. The clinical trials speak for themselves.
There are a couple of other strategies as well. Like using bacterial toxins to boost the immune response etc. but since i don't know much about them, i won't go into the details.
anyway, that was that for MS vaccination. Over all i think prophylactic or therapeutic vaccination against autoimmune diseases are perfectly valid strategies. But i guess if we want to dive into immune modulation as a therapeutic method, first we have to learn a lot more about the immune system as a whole and its complex communication web (with itself and other organs/tissues). But that is exactly what we are doing...so...fight the power you immunologists.
one day my friends...one day.
Sunday, February 4, 2007
dunno
it's 3 am and i wanna go to be-he-ed. gotta lady, runnin' through my he-he-head.
well. i am dosing off at my lap top. i think that is a sign that i should leave and go to bed.
i was at a crowded party tonight, where people knew enough people to feel comfortable but at the same time they didn't know enough people so that every one was eager to have a conversation and introduce themselves. I met many people.
yeah sure it was fun over all.
well. i am dosing off at my lap top. i think that is a sign that i should leave and go to bed.
i was at a crowded party tonight, where people knew enough people to feel comfortable but at the same time they didn't know enough people so that every one was eager to have a conversation and introduce themselves. I met many people.
yeah sure it was fun over all.
Subscribe to:
Comments (Atom)