MTP-I

Microsomal triglyceride transfer protein Inhibitors (MTP-I) represent a new class of cholesterol and triglyceride lowering agents with the ability to affect the production of lipoproteins in both the liver and intestine.

Mechanism of Action

Microsomal triglyceride transfer protein (MTP) is an intraluminal protein in the endoplasmic reticulum that is essential for the assembly of apolipoprotein B (apo-B) containing lipoproteins. What makes MTP therapy unique when compared to other lipid management therapies is its ability to affect the production of cholesterol in both the liver and intestine.

Microsomal triglyceride transfer protein (MTP) is an intracellular lipid-transfer protein found in the lumen of the endoplasmic reticulum that is responsible for binding and shuttling individual lipid molecules between membranes. Normal concentrations and function of MTP are necessary in the liver and intestine for the proper assembly and secretion of lipoproteins that contain apolipoprotein B (apoB). MTP is responsible for transferring triglycerides (TG) onto apo-B in the assembly of very-low-density lipoprotein (VLDL), the precursor to low density lipoprotein (LDL). MTP binds and shuttles individual lipid molecules from the site of lipid synthesis to the emerging apo-B molecule. If insufficient lipid is transferred, the emerging apo-B is destroyed and lipoprotein secretion is inhibited. Inhibition of MTP activity prevents both hepatic VLDL and intestinal chylomicron secretion, and consequently lowers plasma lipids. This means that compounds that inhibit MTP may have the ability to profoundly reduce serum levels of both cholesterol and TG.

A Promising Agent

Aegerion’s lomitapide is an orally effective, selective inhibitor of MTP. Inhibition of MTP prevents the assembly of apoB-containing lipoproteins in hepatocytes and enterocytes and limits the release of these lipoproteins into the systemic circulation.

Current clinical data suggest that an MTP inhibitor such as Aegerion’s lomitapide can play a significant role in meeting the unmet medical needs of patients with hypercholesterolemia, hypertriglyceridemia, and/or mixed lipid disorders involving both cholesterol and TG and patients refractory to currently available treatments.