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Message: Apabetalone and Alkaline Phosphatase

After reading the upcoming ASN abstracts and reviewing the past publications and presentations about apabetalone and alkaline phosphatase, I am extremely excited about apabetalone's potential in not just cardiovascular disease, but also for cognition, kidney function and other diseases.

There seems to be a solid connection to alkaline phosphatase (as well as inflammation) connected to these diseases. From one of the ASN abstracts (bracket text added by me):"Elevated ALP [alkaline phosphatase] is associated with poorer cognitive function and greater prevalence of CKD [as well as CVD]". "Approximately half of the [BETonMACE CKD sub-study] population showed MoCA score <26 suggesting early cognitive impairment. Lower MoCA score was associated with: a) higher ALP, and, b) with presence of CKD." So these diseases (CVD, cognition, CKD) don't operate independently but seem to cluster together and are associated with alkaline phosphatase levels. In pooled analysis of the Phase 2 trials, the most significant (p<0.0001) effect on reported calcification, lipid and inflammation markers was on alkaline phosphatase. Even more significant than effects on apo-AI, HDL-C, and hsCRP. So maybe, just maybe, there is something to this alkaline phosphatase story........

I've compiled abstracts, publications, presentations and posters below for your weekend enjoyment.

ASN and AHA abstracts:

November 8th: 1048: Apabetalone Lowers Serum Alkaline Phosphatase in CVD Patients with and Without CKD and Improves Cardiovascular Risk

November 8th: 317: Association of Serum Alkaline Phosphatase with CKD and Cognitive Function in Patients with Diabetes and Acute Coronary Syndrome

November 9th: 782: Apabetalone Downregulates Alkaline Phosphatase and Improves Cardiovascular Risk

November 18th: ALP Levels Predict Adverse Cardiovascular Outcomes and Cognitive Impairment in High Risk Patients



Apabetalone lowers serum alkaline phosphatase and improves cardiovascular risk in patients with cardiovascular disease

Apabetalone downregulates factors and pathways associated with vascular calcification

Apabetalone Mediated Epigenetic Modulation is Associated with Favorable Kidney Function and Alkaline Phosphatase Profile in Patients with Chronic Kidney Disease

Benefit of Apabetalone on Plasma Proteins in Renal Disease

Apabetalone, A Selective Bromodomain And Extraterminal (BET) Protein Inhibitor, Reduces Serum FGF23 In Cardiovascular Disease and Chronic Kidney Disease Patients


ERA-EDTA 2018 and 2019 Symposia Presentations (full list here):

A clinical view on BET inhibition in CKD & CVD: Understanding recent data and future perspectives

Targeting residual cardiovascular risk & vascular calcification: The clinical perspective for BET inhibition

The role of ALP as predictor of CV events and vascular calcification in CKD

Cardiovascular disease in diabetes and CKD & residual risk: The promise of epigenetics

Epigenetic mechanisms targeting ALP: A pathway for prevention of vascular calcification?

Epigenetics in CKD: Rationale for BET inhibition, an emerging therapeutic mechanism in renal disease and CVD


BETonMACE CKD Sub-study

BETonMACE Chronic Kidney Disease Sub-Study: Effects of the Selective BET-Inhibitor Apabetalone on Kidney Function and MACE in Post-ACS Patients with Diabetes and Estimated Glomerular Filtration Rate Below 60


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