Abstract

In the past year, we completed a Phase I clinical trial of LCAT. 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 modulate HDL metabolism. We also commenced a long-term animal toxicity study in collaboration with AlphaCore Pharma, our CRADA partner and plan to file IND early next year to begin a clinical trial treating patients with a genetic deficiency of LCAT. We are also planning on doing a clinical study on monitoring the flux of cholesterol after recombinant LCAT treatment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006092-03
Application #
8558032
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$663,169
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Sakurai, Toshihiro; Sakurai, Akiko; Vaisman, Boris L et al. (2018) Development of a novel fluorescent activity assay for lecithin:cholesterol acyltransferase. Ann Clin Biochem 55:414-421
Cooke, Allison L; Morris, Jamie; Melchior, John T et al. (2018) A thumbwheel mechanism for APOA1 activation of LCAT activity in HDL. J Lipid Res 59:1244-1255
Freeman, Lita A; Demosky Jr, Stephen J; Konaklieva, Monika et al. (2017) Lecithin:Cholesterol Acyltransferase Activation by Sulfhydryl-Reactive Small Molecules: Role of Cysteine-31. J Pharmacol Exp Ther 362:306-318
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
Thacker, Seth G; Rousset, Xavier; Esmail, Safiya et al. (2015) Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice. J Lipid Res 56:1282-95
Stukas, Sophie; Freeman, Lita; Lee, Michael et al. (2014) LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice. J Lipid Res 55:1721-9
Liu, Zheng; Thacker, Seth G; Fernandez-Castillejo, Sara et al. (2014) Synthesis of cholesterol analogues bearing BODIPY fluorophores by Suzuki or Liebeskind-Srogl cross-coupling and evaluation of their potential for visualization of cholesterol pools. Chembiochem 15:2087-96
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

Showing the most recent 10 out of 19 publications