Antisense therapy in the treatment of hypercholesterolemia

Giuseppe Lippi, Emmanuel J Favaloro

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)


Cardiovascular disease, the leading causes of death worldwide, is a "preventable" pathology, so that accessible and affordable interventions should be established to target the leading risk factors, including hypercholesterolemia. Although statin based therapy is commonplace in primary and secondary prevention, several economical, clinical and safety issues have been raised, so that there is ongoing research into new, safer and more effective agents to be used alone or in combination with existing cardiovascular drugs. Antisense oligonucleotides (ASOs) are a class of short, single-stranded synthetic analogs of nucleic acids that bind to a target mRNA, preventing its translation and thereby inhibiting protein synthesis. Apolipoprotein B-100 (apoB-100) is the major protein moiety of the atherogenic lipoproteins LDL and Lp(a), thus representing the ideal target for antisense therapy. Two anti-apoB100 (i.e., ISIS 301012 and ISIS 147764) and one anti-apolipoprotein(a) (i.e., ASO 144367) have already been developed and tested in some animal and human trials, providing promising results in terms of significant reduction of both LDL and Lp(a). Nevertheless, some safety issues - especially injection-site reactions and potential hepatotoxicity - have also emerged, thereby slowing down the large clinical diffusion of these agents. The present article provides an update on clinical data regarding antisense therapy targeting human apolipoproteins, highlighting the benefits and the potential risks of this innovative therapeutic approach for hypercholesterolemia and hyperlipoproteinemia(a).

Original languageEnglish
Pages (from-to)541-546
Number of pages6
JournalEuropean Journal of Internal Medicine
Issue number6
Publication statusPublished - Dec 2011


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