In the past year, we completed the analysis of samples from a Phase I clinical trial of recombinant LCAT (rLCAT), which we completed in the fall of 2012. The study was done at the NIH and was a single dose escalation study in 18 subjects. There was no significant adverse events and the the recombinant LCAT behaved like expected based on animal studies in regard to its ability to increase HDL levels. We were also granted approval for a single patient IND for the treatment of a patient with Familial LCAT Deficiency (FLD) with rLCAT. The rLCAT treatment restored cholesteryl ester levels to near normal levels and above threshold necessary to prevent LpX formation, the abnormal lipoprotein particle that accumulates in FLD and causes renal disease. The rLCAT treatment also corrected the other lipoprotein abnormalities in this disorder, such as low HDL, which may contribute to cardiovascular disease.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$1,065,405
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Shamburek, Robert D; Bakker-Arkema, Rebecca; Auerbach, Bruce J et al. (2016) Familial lecithin:cholesterol acyltransferase deficiency: First-in-human treatment with enzyme replacement. J Clin Lipidol 10:356-67
Ossoli, Alice; Neufeld, Edward B; Thacker, Seth G et al. (2016) Lipoprotein X Causes Renal Disease in LCAT Deficiency. PLoS One 11:e0150083
Shamburek, Robert D; Bakker-Arkema, Rebecca; Shamburek, Alexandra M et al. (2016) Safety and Tolerability of ACP-501, a Recombinant Human Lecithin:Cholesterol Acyltransferase, in a Phase 1 Single-Dose Escalation Study. Circ Res 118:73-82
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Stukas, Sophie; Freeman, Lita; Lee, Michael et al. (2014) LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice. J Lipid Res 55:1721-1729
Vaisman, Boris L; Remaley, Alan T (2013) Measurement of lecithin-cholesterol acyltransferase activity with the use of a Peptide-proteoliposome substrate. Methods Mol Biol 1027:343-52
Hoang, Anh; Drew, Brian G; Low, Hann et al. (2012) Mechanism of cholesterol efflux in humans after infusion of reconstituted high-density lipoprotein. Eur Heart J 33:657-65
Rosenson, Robert S; Brewer Jr, H Bryan; Davidson, W Sean et al. (2012) Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125:1905-19
Rosenson, Robert S; Brewer Jr, H Bryan; Chapman, M John et al. (2011) HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem 57:392-410

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