At the Hyderabad edition of the TNQ’s Distinguished Lectures in Life Sciences, Geneticist Helen Hobbs told an audience of scientists shared her story of the discovery of cholesterol-lowering mutations in a human gene called 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.
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