Brian R Krause1, Alan T Remaley. 1. aAlphaCore Pharma, Ann Arbor, Michigan bLipoprotein Metabolism Section, Cardiopulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Abstract
PURPOSE OF REVIEW: New therapeutic strategies are needed for the rapid stabilization of acute coronary syndrome (ACS) patients by treating nonculprit lesions. Reconstituted HDL (rHDL), which is apoA-I combined with phospholipids, is currently being tested in clinical trials for this purpose and is the subject of this review. RECENT FINDINGS: At least four different formulations (SRC-rHDL, CSL-111, CSL-112 and ETC-216) have been tested in clinical trials. The various rHDL preparations have been shown to be effective in the rapid mobilization of excess cholesterol from cells and in regressing atherosclerotic plaques in animal models. Two of the rHDL agents, namely ETC-216 and CSL-111, have been shown to be effective after only a few treatments in reducing plaque volume in ACS patients, as assessed by intravascular ultrasound, but no clinical trials assessing clinical endpoints have yet been completed. SUMMARY: rHDL is a promising new potential therapy for ACS patients, but much work remains to be done, and there are many unresolved questions. Progress in developing rHDL into a therapy will depend on improving our understanding of their mechanism of action, determining the optimum formulation and delivery and how to monitor rHDL therapy.
PURPOSE OF REVIEW: New therapeutic strategies are needed for the rapid stabilization of acute coronary syndrome (ACS) patients by treating nonculprit lesions. Reconstituted HDL (rHDL), which is apoA-I combined with phospholipids, is currently being tested in clinical trials for this purpose and is the subject of this review. RECENT FINDINGS: At least four different formulations (SRC-rHDL, CSL-111, CSL-112 and ETC-216) have been tested in clinical trials. The various rHDL preparations have been shown to be effective in the rapid mobilization of excess cholesterol from cells and in regressing atherosclerotic plaques in animal models. Two of the rHDL agents, namely ETC-216 and CSL-111, have been shown to be effective after only a few treatments in reducing plaque volume in ACS patients, as assessed by intravascular ultrasound, but no clinical trials assessing clinical endpoints have yet been completed. SUMMARY: rHDL is a promising new potential therapy for ACS patients, but much work remains to be done, and there are many unresolved questions. Progress in developing rHDL into a therapy will depend on improving our understanding of their mechanism of action, determining the optimum formulation and delivery and how to monitor rHDL therapy.
Authors: Robert D Shamburek; Rebecca Bakker-Arkema; Alexandra M Shamburek; Lita A Freeman; Marcelo J Amar; Bruce Auerbach; Brian R Krause; Reynold Homan; Steve J Adelman; Heidi L Collins; Maureen Sampson; Anna Wolska; Alan T Remaley Journal: Circ Res Date: 2015-12-01 Impact factor: 17.367
Authors: David B Altshuler; Padma Kadiyala; Felipe J Nuñez; Fernando M Nuñez; Stephen Carney; Mahmoud S Alghamri; Maria B Garcia-Fabiani; Antonela S Asad; Alejandro J Nicola Candia; Marianela Candolfi; Joerg Lahann; James J Moon; Anna Schwendeman; Pedro R Lowenstein; Maria G Castro Journal: Expert Opin Biol Ther Date: 2020-01-20 Impact factor: 4.388
Authors: Lita A Freeman; Stephen J Demosky; Monika Konaklieva; Rostislav Kuskovsky; Angel Aponte; Alice F Ossoli; Scott M Gordon; Ross F Koby; Kelly A Manthei; Min Shen; Boris L Vaisman; Robert D Shamburek; Ajit Jadhav; Laura Calabresi; Marjan Gucek; John J G Tesmer; Rodney L Levine; Alan T Remaley Journal: J Pharmacol Exp Ther Date: 2017-06-02 Impact factor: 4.030