LONGECITY

Ran across this article yesterday, seems quite impressive from what I understand. Full text can be found here: http://www.pnas.org/...1604032113.full

Overall substantial clearance of soluble Aβ levels and plaques via recruitment/facilitation of microglial phagocytosis and increased uptake by myeloid cells. On the behavioral side, IL-33 significantly increased exploratory behavior in open field paradigm, and effectively ameliorated memory retrieval deficits as observed in context dependent fear conditioning- presumably by normalizing LTP impairments. Lastly, it down regulates other pro-inflammatory cytokines and associated genes of IL-1β (G), and IL-6 (H), reducing global inflammation.

Abstract:

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

While all results/data were from an APP/PS1 mouse model within the methods section, towards the bottom, it mentions human subjects...strange

Well, here's the rub. Looking at the doses employed with the mine of 200 ng this would translate roughly to 20 ug/kg, assuming there's not some drastic translation effect to humans this is well outside any normal individual's budget. 

Just for fun... with an average human weight of 80.7 you would effectively require 1.614 mg for each day. That's depending on your source, in this case $2,300/ 500ug (biolegend) - $7,424 a day or about ~15k for two days as used in the study.  

Well, here's the rub. Looking at the doses employed with the mine of 200 ng this would translate roughly to 20 ug/kg, assuming there's not some drastic translation effect to humans this is well outside any normal individual's budget. 

 

Just for fun... with an average human weight of 80.7 you would effectively require 1.614 mg for each day. That's depending on your source, in this case $2,300/ 500ug (biolegend) - $7,424 a day or about ~15k for two days as used in the study.  

Opps the 1.614 is for two days not one...Just caught that. 

thanks for that ... looks really interesting and I am doing some research for my (step)father.

This looks like a very promising compound.

Keen to see any first hand experiences apart from this paper.