PCSK9

About: 

• Geneticist Helen Hobbs’ work on coronary heart disease (CAD) led to the development of PCSK9 inhibitors – the most powerful cholesterol-lowering drugs to hit the market since statins. 
  
  
• These drugs fight the PCSK9 protein, which prevents “bad” low density lipoprotein (LDL) cholesterol from being removed from blood. 
  
  

Background: 

• In the mid-2000s, Dr. Helen Hobbs found that a mutation in the PCSK9 gene, present mainly in African Americans, suppressed LDL levels. Consequently, it protected carriers from CAD. 
  
  
• Importantly, people with two copies of this mutation had no side-effects of very low LDL, such as loss of adrenal function. 
  
  
• Most scientists then were carrying out genome-wide association studies (GWAS), which look for common gene variants. Unfortunately, this strategy had mainly identified gene variants with a small impact on CAD risk. 
  
  
• A key innovation in Dr. Hobbs’ approach was to look for a rare gene variation with a large impact on cholesterol. She discovered rare mutations in the PCSK9 gene. 
  
  
• Eventually, drugmakers Amgen and Regeneron developed the PCSK9 inhibitors Evolocumab and Alirocumab, respectively, which mimic this mutation’s effects. 
  
  
• The discovery of cholesterol-lowering mutations in a human gene called PCSK9 led to the development of the most promising new drugs against heart disease since statins. 
  
  
• For her discovery, she won a 2016 Breakthrough Prize in Life Sciences and the 2018 Harrington Prize for Innovation in Medicine.