Daniel Gaudet, M http://forzest.org .D., Ph.D., Veronica J. Alexander, Ph.D., Brenda F. Baker, Ph.D., Diane Brisson, Ph.D., Karine Tremblay, Ph.D., Walter Singleton, M.D., Richard S. Geary, Ph.D., Steven G. Hughes, M.B., B.S., Nicholas J. Viney, B.Sc., Mark J. Graham, M.S., Rosanne M. Crooke, Ph.D., Joseph L. Witztum, M.D., John D. Brunzell, M.D., and John J.P. Kastelein, M.D., Ph.D.: Antisense Inhibition of Apolipoprotein C-III in Individuals with Hypertriglyceridemia Elevated triglyceride levels are associated with many pathologic conditions, including insulin level of resistance, the metabolic syndrome, diabetes, cardiovascular disease, and hereditary disorders, such as the familial chylomicronemia syndrome, familial mixed hyperlipidemia, and familial hypertriglyceridemia.1,2 Patients with triglyceride amounts above 2000 mg per deciliter , measured at the peak of abdominal pain, are at high risk for pancreatitis.3,4 Current suggestions from the Endocrine Culture and the European Atherosclerosis Society advise that fasting triglyceride amounts ought to be maintained at ideals below 1000 mg per deciliter or 10 mmol per liter, respectively, to prevent intermittent increases in triglyceride levels at which pancreatitis may appear.1,2 At moderate-to-high elevations in triglyceride amounts, patients may also be at risk for fresh events of coronary heart disease or for recurrence of occasions in established coronary disease.5-10 Apolipoprotein C-III is a key regulator of lipoprotein fat burning capacity and has a pivotal role in regulating plasma triglyceride levels.11,12 It is synthesized principally in the liver and is an element of triglyceride-rich lipoproteins.15-20 At higher concentrations, APOC3 inhibits the experience of hepatic lipase also,21 an enzyme that plays an important role in the conversion of very-low-density lipoprotein to intermediate-density lipoprotein and low-density lipoprotein ,22 in addition to in the remodeling of high-density lipoprotein .23 Thus, elevated levels of APOC3 in plasma have been connected with both impaired lipolysis and impaired clearance of triglyceride-rich lipoproteins from the circulation.
Flushing and gastrointestinal events were of moderate or moderate severity for some patients; the incidence of the events was in the first month of the study highest, reducing thereafter . Adverse occasions reported more often in the glatiramer acetate group than in the placebo group were injection-related events: injection-site pain and injection-site erythema . Infections were reported in 56 percent of patients in both BG-12 groups and 50 percent of sufferers in the placebo and glatiramer acetate organizations. Infections with an incidence that was at least 2 %age points higher in either BG-12 group than in the placebo group included nasopharyngitis, urinary tract infection, upper respiratory tract infection, bronchitis, sinusitis, and gastroenteritis.