How Do ApoB Antisense Oligonucleotides Work?

Lipid-lowering agents also known as cholesterol-lowering, hypolipidemic, or antihyperlipidemic agents are a group of drugs used to reduce high levels of lipids (fats) and lipoproteins (fats with protein) in the blood. These drugs are used to treat cardiovascular abnormalities such as atherosclerosis (build-up of fats and other substances in the wall of arteries, causing obstruction of blood flow) and decrease the risk of potential heart attacks. Lipid-lowering agents include:

• Apolipoprotein B (ApoB) antisense oligonucleotides
• Adenosine triphosphate citrate lyase inhibitors
• 2-Azetidiones
• Microsomal triglyceride transfer protein inhibitors
• Statins (β-hydroxy β-methylglutaryl-CoA reductase inhibitor)
• Fibrates
• Bile acid sequestrants
• Omega 3 acids
• Vitamin B3

Apo B antisense oligonucleotides are a new class of drugs that reduce the production of ApoB-100 in the liver cells, which are principal lipoproteins of low-density lipoprotein (LDL, bad cholesterol) and essential for the synthesis of very-low-density lipoprotein (VLDL).

During the formation of lipoproteins, Apo B-100 genes present in the liver cells are converted from DNA into mRNA and the mRNA formed is further converted into ApoB-100. ApoB antisense oligonucleotides bind to the mRNA and prevent the formation of ApoB-100. Therefore, these drugs reduce the levels of LDL, non-high-density lipoprotein cholesterol, total cholesterol, and ApoB in the blood.

ApoB antisense oligonucleotides are injectables, given subcutaneously, and used to treat conditions such as:

• Homozygous familial hypercholesterolemia (a life-threatening genetic condition that causes extremely high levels of LDL cholesterol in the body)
• Familial chylomicronemia syndrome also known as type I hyperlipoproteinemia (an inherited disease where people have abnormally high levels of some types of fat called triglycerides in their blood)
• Partial lipodystrophy (a condition in which the distribution of fat in the fat tissue is abnormal)

Common side effects of ApoB antisense oligonucleotides include:

• Nausea and vomiting
• Thrombocytopenia (decrease in platelet count)
• Abdominal pain
• Flu-like symptoms
• Fever
• Reactions such as swelling, itching, or bruising at the site of injection
• Headache

Serious side effects of ApoB antisense oligonucleotides may include:

• Hypersensitivity reaction)
• Liver damage
• Increased liver enzymes
• Increased bilirubin levels
• Fatty liver disease
• Pancreatitis (inflammation of the pancreas)
• Chest pain
• Palpitations
• Hypertension (increase in blood pressure)
• Edema
• Xanthomas (formation of yellow fatty deposits just under the skin, generally around joints)

The information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of ApoB antisense oligonucleotides drugs include:

• Kynamro (Mipomersen)
• Volanesorsen (Waylivra)