December 3, 2014Open Access
View Full PaperTargeting APOC3 in the Familial Chylomicronemia Syndrome
Structured PICO
Does ISIS 304801 reduce plasma APOC3 and triglyceride levels in patients with familial chylomicronemia syndrome?
P
Population
3 patients with familial chylomicronemia syndrome and baseline triglyceride levels ranging from 1406 to 2083 mg per deciliter
I
Intervention
ISIS 304801 (inhibitor of APOC3 mRNA) administered for 13 weeks
O
Outcome
Plasma APOC3 levels and triglyceride levels at 13 weekssurrogate
Inhibition of APOC3 mRNA with ISIS 304801 substantially reduces triglyceride levels in patients with familial chylomicronemia syndrome, demonstrating that APOC3 regulates triglyceride metabolism through LPL-independent pathways.
Abstract
The familial chylomicronemia syndrome is a genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis due to a deficiency in lipoprotein lipase (LPL). Currently, there are no effective therapies except for extreme restriction in the consumption of dietary fat. Apolipoprotein C-III (APOC3) is known to inhibit LPL, although there is also evidence that APOC3 increases the level of plasma triglycerides through an LPL-independent mechanism. We administered an inhibitor of APOC3 messenger RNA (mRNA), called ISIS 304801, to treat three patients with the familial chylomicronemia syndrome and triglyceride levels ranging from 1406 to 2083 mg per deciliter (15.9 to 23.5 mmol per liter). After 13 weeks of study-drug administration, plasma APOC3 levels were reduced by 71 to 90% and triglyceride levels by 56 to 86%. During the study, all patients had a triglyceride level of less than 500 mg per deciliter (5.7 mmol per liter) with treatment. These data support the role of APOC3 as a key regulator of LPL-independent pathways of triglyceride metabolism.