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Details on Person Apolipoprotein B is a major protein constituent of chylomicr...
| Class:Id | Summation:9737661 |
|---|---|
| _displayName | Apolipoprotein B is a major protein constituent of chylomicr... |
| _timestamp | 2021-07-21 09:35:49 |
| created | [InstanceEdit:9737613] Jassal, Bijay, 2021-07-21 |
| literatureReference | [LiteratureReference:9737646] Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial [LiteratureReference:9737629] Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials [LiteratureReference:9737669] Mipomersen sodium: first global approval [LiteratureReference:9737653] Efficacy and safety of mipomersen in treatment of dyslipidemia: a meta-analysis of randomized controlled trials |
| text | Apolipoprotein B is a major protein constituent of chylomicrons, LDL and VLDL. Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically high levels of LDL, in the blood and early cardiovascular disease. About 1 in 150 people have mutations in the LDLR gene that encodes the LDL receptor, which normally removes LDL from the circulation, or APOB, which is the part of LDL that binds with LDLR. People who have one abnormal copy (heterozygous) of the LDLR gene may develop premature cardiovascular disease (age 30-40). Having two abnormal copies (homozygous) may cause severe cardiovascular disease in childhood. Heterozygous FH is a much more common genetic disorder than homozygous FH. Antisense oligonucleotides (ASOs) are single-stranded chemically modified nucleic acid polymers that when bound to the target RNA sequence, the RNA can be degraded, hindered, or manipulated by alternative splicing (Gagliardi & Ashizawa 2021). Mipomersen is a second-generation ASO targeting apolipoprotein B (APOB) mRNA (Yu et al. 2008). Once bound, the resultant drug:RNA complex recruits ribonuclease H1 (RNaseH1), an endonuclease that cleaves the phosphodiester bonds of RNA, subsequently degrading it. The ultimate consequence of this is that less APOB protein is produced so less LDLs and VLDLs are synthesized. Mipomersen is used for the treatment of homozygous FH (Hair et al. 2013), a rare genetic disorder characterized by high levels of low density lipoprotein cholesterol (LDL-C). In clinical trials, mipomersen has demonstrated significant dose-dependent reductions in all measured APOB-containing atherogenic lipoproteins (Raal et al. 2010, Santos et al. 2015). Due to a serious risk of liver toxicity (Panta et al. 2015), mipomersen is only available to patients under a restricted program. |
| (summation) | [Reaction:9737634] APOB mRNA binds mipomersen [Homo sapiens] |
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