In January 2013, the FDA approved mipomersen (Kynamro, Genzyme), an antisense oligonucleotide inhibitor of apo B, as an orphan drug for the management of HoFH (homozygous familial hypercholesterolemia). Mipomersen is indicated as an adjunct therapy to lipid-lowering agents and to lifestyle changes for reducing LDL-C (colesterol LDL), apo B (apolipoprotein B), TC (total colesterol), and non–HDL-C (colesterol HDL) levels.
Mipomersen is an antisense oligonucleotide inhibitor of apo B-100 synthesis, an essential component of lipoproteins such as very-low-density lipoprotein (VLDL) and LDL. This novel technology utilizes short, single-stranded synthetic DNA molecules to target and complement a specific messenger RNA (mRNA) sequence responsible for coding apo B-100. The hybridized mipomersen and mRNA molecule results in the activation of RNase H, an enzyme that catalyzes RNA cleavage, and inhibition of protein translation to decrease apo B concentrations. Ultimately, the production of atherogenic lipoproteins is decreased.
At the moment of the FDA approval, it was a breakthrough for the FH homozygous patients since to the date no other drugs or statins presented a good disease outcome rate. But mipomersen is not only indicated for homozygous FH patients but also for heterozygous with severe autosomal dominant mutations in the LDLR gene (LDLR gene).
Gene or region studied