I was doing a little digging into Alzheimer’s a
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Posted On: 11/01/2020 1:44:44 AM
I was doing a little digging into Alzheimer’s and how Leronlimab could help but ended back to HIV again. I stumbled across this, must have missed it last time I googled CCR5 and checked out wiki. Maybe someone smarter can explain why Leronlimab won’t run into this problem or hasn’t already with HIV. Or this just is not accurate information.
“These experimental drugs include PRO140 (CytoDyn), Vicriviroc (Phase III trials were cancelled in July 2010) (Schering Plough), Aplaviroc (GW-873140) (GlaxoSmithKline) and Maraviroc (UK-427857) (Pfizer). Maraviroc was approved for use by the FDA in August 2007.[27] It is the only one thus far approved by the FDA for clinical use, thus becoming the first CCR5 inhibitor.[25] A problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another co-receptor (CXCR4), but persisted in using CCR5: they either bound to alternative domains of CCR5 or to the receptor at a higher affinity.
[However, because there is still another co-receptor available, it is probable that lacking the CCR5 gene does not make one immune to the virus; it would simply be more challenging for the individual to contract it. Also, the virus still has access to CD4. Unlike CCR5, which is not required (as evidenced by those living healthy lives even when lacking the gene as a result of the delta32 mutation), CD4 is critical in the body's immune defense system.[29] Even without the availability of either co-receptor (even CCR5), the virus can still invade cells if gp41 were to go through an alteration (including its cytoplasmic tail) that resulted in the independence of CD4 without the need of CCR5 and/or CXCR4 as a doorway]”
Gp41 an issue maybe for prep or a small sub population?
Maybe I misread this or this is where a few patients might not respond to Leronlimab if Gp41 alterations occur.
https://en.m.wikipedia.org/wiki/CCR5
“These experimental drugs include PRO140 (CytoDyn), Vicriviroc (Phase III trials were cancelled in July 2010) (Schering Plough), Aplaviroc (GW-873140) (GlaxoSmithKline) and Maraviroc (UK-427857) (Pfizer). Maraviroc was approved for use by the FDA in August 2007.[27] It is the only one thus far approved by the FDA for clinical use, thus becoming the first CCR5 inhibitor.[25] A problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another co-receptor (CXCR4), but persisted in using CCR5: they either bound to alternative domains of CCR5 or to the receptor at a higher affinity.
[However, because there is still another co-receptor available, it is probable that lacking the CCR5 gene does not make one immune to the virus; it would simply be more challenging for the individual to contract it. Also, the virus still has access to CD4. Unlike CCR5, which is not required (as evidenced by those living healthy lives even when lacking the gene as a result of the delta32 mutation), CD4 is critical in the body's immune defense system.[29] Even without the availability of either co-receptor (even CCR5), the virus can still invade cells if gp41 were to go through an alteration (including its cytoplasmic tail) that resulted in the independence of CD4 without the need of CCR5 and/or CXCR4 as a doorway]”
Gp41 an issue maybe for prep or a small sub population?
Maybe I misread this or this is where a few patients might not respond to Leronlimab if Gp41 alterations occur.
https://en.m.wikipedia.org/wiki/CCR5
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