Familial lecithin:cholesterol acyltransferase deficiency: First-in-human treatment with enzyme replacement.
J Clin Lipidol
; 10(2): 356-67, 2016.
Article
en En
| MEDLINE
| ID: mdl-27055967
ABSTRACT
BACKGROUND:
Humans with familial lecithincholesterol acyltransferase (LCAT) deficiency (FLD) have extremely low or undetectable high-density lipoprotein cholesterol (HDL-C) levels and by early adulthood develop many manifestations of the disorder, including corneal opacities, anemia, and renal disease.OBJECTIVE:
To determine if infusions of recombinant human LCAT (rhLCAT) could reverse the anemia, halt progression of renal disease, and normalize HDL in FLD.METHODS:
rhLCAT (ACP-501) was infused intravenously over 1 hour on 3 occasions in a dose optimization phase (0.3, 3.0, and 9.0 mg/kg), then 3.0 or 9.0 mg/kg every 1 to 2 weeks for 7 months in a maintenance phase. Plasma lipoproteins, lipids, LCAT levels, and several measures of renal function and other clinical labs were monitored.RESULTS:
LCAT concentration peaked at the end of each infusion and decreased to near baseline over 7 days. Renal function generally stabilized or improved and the anemia improved. After infusion, HDL-C rapidly increased, peaking near normal in 8 to 12 hours; analysis of HDL particles by various methods all revealed rapid sequential disappearance of preß-HDL and small α-4 HDL and appearance of normal α-HDL. Low-density lipoprotein cholesterol increased more slowly than HDL-C. Of note, triglyceride routinely decreased after meals after infusion, in contrast to the usual postprandial increase in the absence of rhLCAT infusion.CONCLUSIONS:
rhLCAT infusions were well tolerated in this first-in-human study in FLD; the anemia improved, as did most parameters related to renal function in spite of advanced disease. Plasma lipids transiently normalized, and there was rapid sequential conversion of small preß-HDL particles to mature spherical α-HDL particles.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfatidilcolina-Esterol O-Aciltransferasa
/
Deficiencia de la Lecitina Colesterol Aciltransferasa
Límite:
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Clin Lipidol
Asunto de la revista:
BIOQUIMICA
/
METABOLISMO
Año:
2016
Tipo del documento:
Article