High density lipoprotein future or investigational therapies: Difference between revisions
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This methods aim at directly increasing the serum levels of HDL through the infusion of reconstituted and recombinant preparations of HDLs (rHDLs). Recombinant HDLs are made from apo A-1 derived from cellular expression systems while recombinant HDLs are apo A-1 derived from human. Both preparations have been complexed with [[phospholipids]]. The reconstituted forms are relatively cheaper and easier to produce. | This methods aim at directly increasing the serum levels of HDL through the infusion of reconstituted and recombinant preparations of HDLs (rHDLs). Recombinant HDLs are made from apo A-1 derived from cellular expression systems while recombinant HDLs are apo A-1 derived from human. Both preparations have been complexed with [[phospholipids]]. The reconstituted forms are relatively cheaper and easier to produce. | ||
====ApoA-1 Milano==== | ====ApoA-1 Milano==== | ||
Some individuals in rural Italy were identified with a genetic variant of apo A-1 which conferred some protection against atherosclerosis despite the presence of very low HDL levels (10-30 mg/dl), elevated plasma LDL, and moderate hypertriglyceridemia. | Some individuals in rural Italy were identified with a genetic variant of apo A-1 which conferred some protection against atherosclerosis despite the presence of very low HDL levels (10-30 mg/dl), elevated plasma LDL, and moderate hypertriglyceridemia.<ref name="Sirtori-2001">{{Cite journal | last1 = Sirtori | first1 = CR. | last2 = Calabresi | first2 = L. | last3 = Franceschini | first3 = G. | last4 = Baldassarre | first4 = D. | last5 = Amato | first5 = M. | last6 = Johansson | first6 = J. | last7 = Salvetti | first7 = M. | last8 = Monteduro | first8 = C. | last9 = Zulli | first9 = R. | title = Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study. | journal = Circulation | volume = 103 | issue = 15 | pages = 1949-54 | month = Apr | year = 2001 | doi = | PMID = 11306522 }}</ref> Studies indicated that intravenous infusion recombinant apoA-I Milano (ETC-216) promotes regression of atherosclerosis lesion to a greater extent than wild type apoA-I as measured by intravascular ultrasound within 5 weeks of treatment.<ref name="Nissen-2003">{{Cite journal | last1 = Nissen | first1 = SE. | last2 = Tsunoda | first2 = T. | last3 = Tuzcu | first3 = EM. | last4 = Schoenhagen | first4 = P. | last5 = Cooper | first5 = CJ. | last6 = Yasin | first6 = M. | last7 = Eaton | first7 = GM. | last8 = Lauer | first8 = MA. | last9 = Sheldon | first9 = WS. | title = Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. | journal = JAMA | volume = 290 | issue = 17 | pages = 2292-300 | month = Nov | year = 2003 | doi = 10.1001/jama.290.17.2292 | PMID = 14600188 }}</ref> | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The Need
The importance of increasing serum levels and functionality of HDL-C in lowering residual cardiovascular risks in patients with acute coronary syndromes cannot be over-emphasized. First of all, some recent studies reported failures of orally active medications that increase serum levels of HDL-C to potentially improve cardiovascular outcomes, such as niacin in the AIM-HIGH Trial. This have shifted the focus of researchers to other targets of HDL therapy aimed at increasing the serum levels of HDL as well as its functionality i.e., cellular cholesterol efflux and HDL-mediated reverse cholesterol transport mechanisms. Secondly, since the available oral medications elevate HDL over weeks to months, there is the need for medications which rapidly improve outcomes during acute vascular events.
Direct Infusion of Apo A-1
This methods aim at directly increasing the serum levels of HDL through the infusion of reconstituted and recombinant preparations of HDLs (rHDLs). Recombinant HDLs are made from apo A-1 derived from cellular expression systems while recombinant HDLs are apo A-1 derived from human. Both preparations have been complexed with phospholipids. The reconstituted forms are relatively cheaper and easier to produce.
ApoA-1 Milano
Some individuals in rural Italy were identified with a genetic variant of apo A-1 which conferred some protection against atherosclerosis despite the presence of very low HDL levels (10-30 mg/dl), elevated plasma LDL, and moderate hypertriglyceridemia.[1] Studies indicated that intravenous infusion recombinant apoA-I Milano (ETC-216) promotes regression of atherosclerosis lesion to a greater extent than wild type apoA-I as measured by intravascular ultrasound within 5 weeks of treatment.[2]
CSL-112
CER-001
Cholesterol Ester Transfer Protein (CETP) Inhibition
CETi-1 Vaccine
JTT-705
De-lipidated HDL Infusions
HDL Mimetics
ApoA-1 Mimetic Peptides
- D-4F and L-4F
ATI-5261 Synthetic Peptide
Endothelial Lipase Inhibitors
LCAT Modulators
Endocannabinoid Receptor Blockers
ApoA-1 Upregulators
RVX-208
Synthetic Liver X Receptor (LXR) Agonists
Synthetic FXR Agonists
Gene Therapy
References
- ↑ Sirtori, CR.; Calabresi, L.; Franceschini, G.; Baldassarre, D.; Amato, M.; Johansson, J.; Salvetti, M.; Monteduro, C.; Zulli, R. (2001). "Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study". Circulation. 103 (15): 1949–54. PMID 11306522. Unknown parameter
|month=ignored (help) - ↑ Nissen, SE.; Tsunoda, T.; Tuzcu, EM.; Schoenhagen, P.; Cooper, CJ.; Yasin, M.; Eaton, GM.; Lauer, MA.; Sheldon, WS. (2003). "Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial". JAMA. 290 (17): 2292–300. doi:10.1001/jama.290.17.2292. PMID 14600188. Unknown parameter
|month=ignored (help)