Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. C URRENT O PINION Recent advances in the treatment of homozygous familial hypercholesterolaemia Adrian D. Marais a and Dirk J. Blom b Purpose of review To review publications in the English literature over the past 18 months relating to the management of homozygous familial hypercholesterolaemia. Recent findings Experience with plasmapheresis has been summarized, guidelines are being introduced to enhance patient care and registries are under consideration to improve analysis of management in this rare but serious disorder. Liver transplantation has been reviewed for its biochemical efficacy, but still does not ensure freedom from vascular complications. For patients without access to plasmapheresis, there is now evidence that high-dose statins do improve the prognosis, but combination therapy with additional agents should still be considered for better outcome. Promising new agents that inhibit LDL production by limiting apolipoprotein B100 synthesis by means of antisense oligonucleotides (mipomersen) or by inhibition of microsomal triacylglycerol transfer protein (lomitapide) have made significant additional LDL reduction possible but are associated with hepatic fat accumulation and long-term safety data is still required. Several other lipid modulating agents and gene therapy are still being explored. Summary The management of homozygous familial hypercholesterolaemia by pharmacological means is improving with agents that limit lipoprotein production but plasmapheresis, generally in combination with additional pharmacological treatment, remains the proven option. Liver transplantation is now less likely to be undertaken owing to improved pharmacological options and prognosis. Keywords antisense oligonucleotides, homozygous familial hypercholesterolaemia, microsomal triglyceride transfer protein inhibitors, plasma cholesterol modifying treatment, plasmapheresis INTRODUCTION Brown and Goldstein [1] were awarded the Nobel Prize for defining the pivotal role of the LDL receptor (LDLR) in regulating plasma LDL cholesterol (LDLC) concentration and proved that LDLR malfunction causes familial hypercholesterolaemia in an hetero- zygous (heFH) or homozygous (hoFH) phenotype. The extremely high risk of premature atherosclerosis in hoFH was first addressed by plasmapheresis, with weekly to fortnightly removal of a large fraction of lipoproteins. Liver transplantation [2] provides nor- mal LDLR genes but incompletely corrects plasma LDL, is limited by shortage of donor organs and requires chronic immunosuppression to avoid rejec- tion. Currently available drugs that modulate lip- oprotein metabolism lack the power to correct the severely elevated LDL in hoFH. Hope remains that the genetic error will be corrected in the future. The past 2 years can be viewed as a watershed in the management of hoFH. New approaches that disrupt LDL production by impairing translation of apoB or impairing lipoprotein assembly are being explored in hoFH. This review will briefly describe hepatocel- lular and plasma cholesterol balance, and how different treatment strategies impact on the dysli- pidaemia of hoFH before placing publications in context. a Chemical Pathology, National Health Laboratory Service and b Internal Medicine, Medical Research Council Cape Heart Group, University of Cape Town, Cape Town, South Africa Correspondence to David Marais, 6.33 Falmouth Building, University of Cape Town Health Science Faculty, Anzio Rd, Observatory 7925, Cape Town, South Africa. Tel: +27 21 406 6192; e-mail: david.marais@ uct.ac.za Curr Opin Lipidol 2013, 24:288–294 DOI:10.1097/MOL.0b013e32836308bc www.co-lipidology.com Volume 24  Number 4  August 2013 REVIEW