A clinical trial has demonstrated the potential for an antisense drug to target and reduce serum levels of apolipoprotein A. This may be a new way to reduce cardiovascular risk.
A study published this month in the Lancet has described a novel treatment to reduce levels of apolipoprotein A, a risk factor for cardiovascular disease. The study tested the safety and effectiveness of an antisense drug designed to target apolipoprotein A, reducing its production in the liver, thereby reducing total serum levels.
The study was conducted at the PAREXEL Clinical Pharmacology Research Unit in the UK. Participants in the study were between the ages of 18 and 65 years, with an apolipoprotein A concentration of at least 25nmol/L. Both a single dose of the drug, ISIS-APO(a)Rx, was assessed, in addition to a multi-dose schedule, over a period of 4 weeks.
The study found that single doses of ISIS-APO(a)Rx did not result in a reduction of plasma apolipoprotein A levels. There were, however reductions in plasma apolipoprotein A seen in participants who received multiple doses of ISIS-APO(a)Rx. The reductions in apolipoprotein A were dose-dependent, reducing from a concentration of 39.6% in participants treated with 100mg, to 77.8%in participants treated with 300mg ISIS-APO(a)Rx. The most common adverse events reported were reactions at the site of the injection.
The authors of the study state that the results support continued development of this drug in clinical trials as a potential treatment to reduce cardiovascular risk in patients with high levels of apolipoprotein A.
Tsimikas, S, Viney, NJ, Hughes, SG, Singleton, W, Graham, MJ, Baker, BF, Burkey, JL, Yang, Q, Marcovina, SM, Geary, RS, Crooke, RM, Witztum, JL. “Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study” Lancet, Published Online: 22 July 2015
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Written by Deborah Tallarigo, PhD