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Message: Top 5 things Apabetalone could correct for our health,...

Bear said:

"Alkaline phosphatase would best fit in the vascular calcification category"

https://escholarship.org/content/qt6xf830zr/qt6xf830zr.pdf

Here is an interesting 2017 review article for those interested in the beneficial and detrimental aspects of ALP activity in the body. The senior author is Mathias Haarhaus, a member of the international panel of renal experts for RVX. ALP is associated with bone mineralization (good) but also with vascular calcification (bad); hence Bear's response above.  But the role of ALP extends into many facets of inflammatory disease states.  Apologies if Bear has linked this article in the past, I have not found a good way to search for publications that have been mentioned on the site.

I also have been wondering if the new patent may involve the use of apabetalone as an ALP-lowering therapeutant.  RVX appears to be building the case that ALP is not simply a useful bystander biomarker of inflammatory disease, but an accomplice (or major perpetrator) in the crime.  High ALP levels are also associated with cancer and fibrotic diseases.  Surprisingly, then, not much research seems to have been done for identifying agents to lower the high circulating level of ALP that accompanies so many disease states and is highly correlated with all-cause mortality (as indicated in the above publication and, I wager, by the results of the BetonMace trial). Haarhaus also foreshadows the possible role of ALP in cognitive decline in the article:

"According to this hypothesis, increased release of membrane-bound endothelial ALP into the circulation caused by increased activity of phospholipase C or D could result in decreased cellular ALP levels and thereby contribute to BBB dysfunction in neurodegenerative diseases such as Alzheimer disease, owing to disturbed transcellular transport. Whether ALP is involved in dysfunction of the endothelial barrier, disturbs BBB function in CKD, or causes arterial stiffness or proteinuria in the kidney and leads to CKD progression has yet to be elucidated."

The article only mentions a single ALP inhibitor (SBI-425) that is not in clinical use yet as far as I could determine, and apabetalone (as an example of a BETi) as possbile drugs for this purpose.  My search didn't lead to other articles on ALP therapeutants, only its use as a biomarker of disease.

It may be a patent on the use of apabetalone for an ALP therapeutant could tie together those 7 important pathways pretty nicely.

Jupe

 

 

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