MIPOMERSEN: A NOVEL THERAPEUTIC DRUG FOR THE TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA, HYPERLIPIDAEMIA, AND HYPERCHOLESTEROLEMIA
Abstract
Familial Hypercholesterolemia (FH) is one of the most common autosomal dominant disorders which exist in either heterozygous form or a homozygous form. These two forms are prevalent in1 in500 and1 ina million population respectively. FH results in premature atherosclerosis; as early as childhood in case of homozygous (HoFH) form and in adults in case of heterozygous (HeFH) form. In case of HoFH both the alleles forLDL-receptor are defective, whereas the mutation in the single allele is the cause for HeFH. Both the forms of the disease are associated with high levels ofLDL-C and lipoprotein (a) in plasma, with high morbidity and mortality rate caused by cardiovascular disease. In several past years, different lipid-lowering drugs like Statins (HMG-coenzyme-A reductase inhibitor), MTTP inhibitor, CETP inhibitors, PCSK9 inhibitor, thyroid mimetics, niacin, bile acid sequestrants and lipid apheresis were administered to patients with FH, to achieve the goal of reducing plasmaLDL-C and lipoprotein (a). However, such drugs proved inefficient to achieve the goals because of several reasons. Mipomersen is a 20 nucleotide antisense oligonucleotide; a novel lipid-lowering therapeutic drug currently enrolled in the treatment of patients with HoFH, HeFH and other forms of hypercholesterolemia. It arrests the synthesis of Apo B100 by targeting Apo B100 mRNA and thus inhibiting the synthesis and release of all Apo B-containing lipoproteins, such as very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low-density lipoprotein (LDL), and non-high-density lipoprotein. It also lowers lipoprotein (a), and ultimately reduces the severity of coronary artery disease and cardiovascular disease.
Keywords: Hypercholesterolemia, Low-density lipoprotein, Mipomersen, Cholesterol, Lipoprotein, Antisense oligonucleotideÂ
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References
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