Investigated treatments for lipoprotein lipase deficiency and related metabolic disorders

Introduction: Monogenic chylomicronemia is a rare, dramatic phenotype caused by bi-allelic mutations within genes governing lipolysis, most frequently LPL, but also APOC2, APOA5, LMF1 and GPIHBP1. Features include life-threatening pancreatitis, together with failure to thrive in childhood, hepatosplenomegaly, lipemia retinalis and eruptive xanthomas. We review recent developments of new treatments for this condition.Areas covered: Traditional therapies for severe hypertriglyceridemia are reviewed, including control of secondary causes, dietary modification, weight loss, and supplementation with omega-3 fatty acids. Current pharmacotherapies include fibrates, niacin, and statins, but these are largely ineffective. Plasmapheresis is generally not recommended as it is not a permanent solution in the absence of more specific or targeted management. Newer medications that have been evaluated in monogenic chylomicronemia include LPL gene therapy, lomitapide and mipomersen. Medications in development include volanesorsen, pradigastat, IONIS-ANGPTL3Rx, evinacumab, and a therapeutic apolipoprotein C-II peptide.Expert opinion: Assuming no unforeseen or off-target adverse effects, at least some of these new targeted medications may soon improve the outlook for patients with monogenic chylomicronemia. Also, because some of these therapies target specific components of the lipolytic network, it may be advantageous to know the precise molecular diagnosis in a particular patient to help guide therapy.