Severe hypertriglyceridemia: Existing and emerging therapies

Area of Science:

• Biochemistry
• Genetics
• Cardiology

Background:

• Severe hypertriglyceridemia (sHTG), with triglyceride levels ≥ 500 mg/dL, is a significant risk factor for acute pancreatitis.
• sHTG arises from genetic defects impacting triglyceride lipolysis, including familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS).
• Traditional sHTG treatments offered limited efficacy and did not reduce cardiovascular events.

Purpose of the Study:

• To review the genetic basis of sHTG and its associated risks.
• To explore the development and efficacy of novel, pathway-specific therapeutics for sHTG.
• To highlight the potential of new treatments to reduce acute pancreatitis and cardiovascular disease events.

Main Methods:

• Review of genetic discoveries related to triglyceride metabolism.
• Analysis of emerging therapeutic targets, including apolipoprotein C-III (apoC-III), angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like protein 4 (ANGPTL4), and fibroblast growth factor-21 (FGF21).
• Evaluation of the clinical potential of these novel agents in managing sHTG phenotypes.

Main Results:

• Genetic research has identified key proteins involved in triglyceride lipolysis and their dysfunction in sHTG.
• Novel therapeutics targeting apoC-III, ANGPTL3, ANGPTL4, and FGF21 demonstrate superior TG-lowering efficacy compared to older treatments.
• These targeted therapies offer a promising approach to managing diverse sHTG phenotypes.

Conclusions:

• Genetic insights have revolutionized the understanding and treatment of sHTG.
• Pathway-specific therapies targeting proteins like apoC-III and ANGPTL3 represent a significant advancement in managing sHTG.
• New treatments hold promise for reducing the risk of acute pancreatitis and atherosclerotic cardiovascular disease events in patients with sHTG.