Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder 
typically caused by mutations in genes for lipoprotein lipase (LPL), 
apolipoprotein C-II (Apo-CII), apolipoprotein A-V (Apo-AV), lipase maturation 
factor 1 (LMF1) and glycosylphosphatidylinositol-anchored high-density 
lipoprotein-binding protein 1 (GPI-HBP1). FCS is associated with severe 
morbidity that includes recurrent pancreatitis and other problems. Effective 
treatment to reliably prevent complications has been unavailable, so there is a 
quest to identify novel interventions to achieve sustained triglyceride lowering 
and prevention of pancreatitis. Apolipoprotein C-III (Apo-CIII) interferes with 
triglyceride clearance by blocking LPL and alternative pathways. Volanesorsen is 
an experimental antisense oligonucleotide that inhibits translation of Apo-CIII 
mRNA, thereby substantially lowering plasma levels of Apo-CIII and 
triglycerides. It is being developed for treatment of patients with FCS and 
refractory hypertriglyceridemia. Data from a variety of clinical trials have 
been very encouraging, with documentation of excellent triglyceride-lowering 
efficacy, but there have been concerns about the risk of drug-related 
thrombocytopenia and bleeding that contributed to the recent decision by the 
Food and Drug Administration (FDA) to not approve the drug for clinical use. 
Clinical trials testing the safety and efficacy of volanesorsen are ongoing, so 
there is hope that the drug ultimately will be approved and available for 
treatment of high-risk patients with FCS.