Question

What is the mechanism by which mipomersen lowers serum cholesterol levels? (A) inhibits microsomal triglyceride transport (B) inhibits cholesterol absorption (C) inhibits cholesterol biosynthesis (D) inhibits apolipoprotein B synthesis (E) increases cholesterol excretion

Short answer

Mipomersen lowers cholesterol by inhibiting apolipoprotein B synthesis, corresponding to option (D).

Step-by-step solution

Understand the Function of Mipomersen

Mipomersen is known as an antisense oligonucleotide that specifically targets the messenger ribonucleic acid (mRNA) involved in the synthesis of a specific protein in the body. This information suggests that mipomersen works at the genetic level to reduce the production of a key protein.

Identify the mRNA Targeted by Mipomersen

Mipomersen targets the mRNA of apolipoprotein B (ApoB), which is an essential component of low-density lipoprotein (LDL). LDL is often referred to as "bad cholesterol" because high levels can lead to a buildup of cholesterol in arteries, causing heart disease and other cardiovascular issues.

Determine the Mechanism Based on Function

Since mipomersen works by reducing the levels of ApoB through inhibiting its synthesis, this leads to a subsequent reduction in the assembly and secretion of LDL particles from the liver, thus lowering serum cholesterol levels.

Match the Mechanism with the Given Options

Reviewing the options available: (A) inhibits microsomal triglyceride transport, (B) inhibits cholesterol absorption, (C) inhibits cholesterol biosynthesis, (D) inhibits apolipoprotein B synthesis, (E) increases cholesterol excretion. We know from Step 3 that mipomersen lowers cholesterol by inhibiting the synthesis of apolipoprotein B.

Confirm the Correct Answer

Based on the analysis, the most appropriate mechanism is (D) inhibits apolipoprotein B synthesis, as this is the direct function of mipomersen.

Key concepts

Apolipoprotein B

Apolipoprotein B, often abbreviated as ApoB, is a protein that's crucial for the metabolism of lipids, or fats, in the body. It plays a key role in the creation and transport of low-density lipoproteins (LDL), which are commonly referred to as "bad cholesterol."
High levels of LDL can lead to plaque buildup in arteries, increasing the risk of heart disease and stroke.
The liver produces ApoB-containing lipoproteins, which help carry cholesterol through the bloodstream.

• Each LDL particle contains a single molecule of ApoB.
• ApoB helps LDL bind to receptors on cell surfaces, which is an essential step in the uptake of cholesterol by cells.
• Hence, managing levels of ApoB is vital for maintaining healthy cholesterol levels and reducing cardiovascular risk.

Interventions, like drugs that inhibit ApoB synthesis, can decrease LDL levels in the blood, leading to better heart health.

Serum Cholesterol Levels

Serum cholesterol levels refer to the amount of cholesterol present in the blood.
Cholesterol is a type of lipid that's vital for the formation of cell membranes, hormones, and vitamin D.
However, too much cholesterol in the bloodstream can be harmful.

• Cholesterol in the blood is carried by lipoproteins, which come in different types: LDL (low-density lipoprotein) and HDL (high-density lipoprotein).
• LDL is often tagged as "bad cholesterol" since it can deposit in the walls of arteries, leading to atherosclerosis.
• In contrast, HDL, or "good cholesterol," helps transport cholesterol away from the arteries to the liver, where it's processed and removed from the body.

Balancing these cholesterol types is crucial for cardiovascular health, and interventions that lower LDL or raise HDL concentrations are beneficial. Serum cholesterol levels can be managed through diet, exercise, and sometimes medications that target specific cholesterol synthesis pathways.

Mechanism of Action

In pharmacology, the "mechanism of action" refers to how a drug produces its effects within the body.
Understanding this process helps explain why a drug is effective for a particular condition.
Mipomersen, the drug in question, works through a genetic approach.

• It targets the messenger RNA (mRNA) that provides instructions for producing apolipoprotein B.
• This interference means less ApoB is produced, resulting in fewer LDL particles entering the bloodstream.
• As a result, serum cholesterol levels drop because there's less "bad cholesterol" circulating in the blood.

The strategic design of such drugs aims at tackling diseases at their biological roots, offering precision in reducing target molecules responsible for disease conditions.

Antisense Oligonucleotide

An antisense oligonucleotide is a short strand of nucleotides, designed to bind to a specific sequence of messenger RNA (mRNA) in cells.
This advanced technology is used to inhibit protein synthesis, and it's at the heart of how mipomersen functions.

• These synthetic strands are designed to be complementary to the mRNA of a target protein, such as apolipoprotein B.
• By binding to the mRNA, the antisense oligonucleotide prevents it from being translated into its corresponding protein.
• Thus, they provide a mechanism to "turn off" the production of certain proteins associated with diseases.

This method of action allows for the reduction of specific harmful proteins, like ApoB, which can then lead to a decrease in disease-related complications. The development and use of antisense oligonucleotides represent a cutting-edge approach in the treatment of genetic and metabolic disorders.