Ohm, I'm very interested in the Alzheimer's study

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Ohm, I'm very interested in the Alzheimer's study as my stepfather was diagnosed about 18 months ago. I know you have explained before so maybe you can point me to one of your older posts, but I don't have as good of an understanding as to how LL is expected to help with this disease as I do with cancer or HIV. Do we think we will actually be able to reverse the effects, or would we just stop the progression?

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Let's start with what the current drugs are targeting the amyloid beta and tau protein entanglements. Maraviroc has been shown to clear them. Scientists for quite a long time thought those entanglements were the cause of Alzheimer's but they're just an offshoot of the real cause. The real cause is inflammation and immune dysregulation.

That inflammation causes a rise in overactive microglia (macrophages that exist in the brain and central nervous system) to go on the attack and kill neurons and synapses. Those same microglia will also damage vascular cells lowering necessary blood flow to the brain. Overactive microglia can also increase tau and beta pathologies. Conversely you do need a moderate amount of normally active microglia to help destroy the beta and tau entanglements. Microglia also shape dendritic spine formation and overactive microglia excessively prune them and destroy branching where synaptic connection occurs. Once again you need a moderate amount of microglial activity for homeostasis and normal dendritic spine formation. As in other diseases involving macrophages, leronlimab would switch the microglia from M1 to M2 but then limit the overactive state due to lowered migration through blocking CCL5 bringing about homeostasis.

In Alzheimer's you'll also see impaired mitochondria. The energy produced from mitochondria is necessary to neuronal signaling. CCR5 blocking can help mitochondria from being destroyed and can help in its repair.

One of the most implicated factors in Alzheimer's is hereditary mutation of the APOE4 gene. The APOE4 gene increases levels of TIMPs (tissue inhibitor of metalloproteinases) which in turn increases MMPs (Matrix metalloproteinases). High levels of MMPs are implicated in tau/beta accumulation, cell death, a leaky blood brain barrier and an increase in inflammatory cytokines. Leronlimab knocks down levels of TIMPs and MMPs.

All of which go toward halting disease progression. I don't think reversal of Alzheimer's with CCR5 blockade has been studied too much. However in other neurological diseases blockade has been shown to increase dendritic spine growth, increase growth of new neurons, increase synaptic transmission and improve brain plasticity. There is a reasonable chance that leronlimab could repair damage in early stage Alzheimer's most likely decreasing in very late stages.