Role of LCAT in HDL remodeling: an investigation in LCAT deficiency states.
In contrast, in LCAT deficiency there is effective cholesterol efflux from cholesterol-loaded macrophages followed by defective maturation of pre-[beta] HDL to [alpha] HDL; accelerated catabolism, primarily of LpAI:AII as well as LpAI; and renal disease, but no increased risk of CVD (125, 126).
AlphaCore Pharma, a biopharmaceutical company developing ACP-501 (rhLCAT) for the treatment of high risk atherosclerosis and serious lipid metabolism disorders, today announced it has received orphan drug designation from the European Medicines Agency (EMA) for ACP-501 for the treatment of familial LCAT deficiency (FLD).
Familial LCAT deficiency is a rare, inherited condition that causes lipid accumulation in the eyes, red blood cells and kidneys.
Consequently, as in Tangier disease, patients with LCAT deficiency
have increased pre-[[beta].
ACP-501 is also being developed to treat familial LCAT deficiency
, as an orphan-designated enzyme replacement therapy, and other conditions where LCAT activity is low.
LCAT deficiency is associated with markedly decreased HDL-C concentrations, whereas LCAT overexpression in mice and rabbits markedly increases HDL-C concentrations.
Importantly, patients with LCAT deficiency and Tangier disease often have decreased LDL-C concentrations, which may be one factor offsetting the low HDL-C concentrations (7, 10).
Additionally, ACP-501 is being developed to treat familial LCAT deficiency
(an orphan designated enzyme replacement therapy) and other diseases where LCAT activity is low.
AlphaCore Pharma, a biopharmaceutical company, and Advanced Bioscience Laboratories (ABL), a biomedical contract research and manufacturing company, today announce funding from the National Institutes of Health, National Heart, Lung and Blood Institute (NHLBI) "Science Moving towards Research Translation and Therapy" (SMARTT) program, to manufacture recombinant human lecithin-cholesterol acyltransferase (rhLCAT) for the treatment of familial LCAT deficiency.
Manufacturing support from the NHLBI SMARTT program will enable production of additional material that will be used to determine the safety and efficacy of rhLCAT enzyme replacement therapy for patients with familial LCAT deficiency - a potentially life-threatening illness for which there is no FDA-approved treatment.