Case Study: Rabbits & Lipitor

Lipitor is a member of the drug class known as statins, used for lowering blood cholesterol. It's considered one of the most successful drugs ever developed in the modern medical era.

Sales of Lipitor have exceeded $125 billion since the drug's approval in 1996, and have stayed near the top of best-selling drug list for nearly a decade. Because of the use of Lipitor and other similar statin drugs, the events of cardiovascular diseases (CVD) in the nation have dropped by approximately one-third.

The development of statin drugs is indebted to rabbits. Lipitor and other statins work by inhibiting HMG-CoA reductase, an enzyme in the LDL receptor pathway that's found in liver tissue and plays a key role in the production of cholesterol in the body.

In the 1970s, when genetically engineered mice were not yet available, a breed of rabbits named WHHL rabbits were used by Goldstein and Brown, and helped them to prove the LDL receptor pathway hypothesis. Goldstein and Brown were awarded the Nobel Prize in 1985 for “their discoveries concerning the regulation of cholesterol metabolism.” In their Award Lecture, rabbits were mentioned and specially acknowledged.

Interestingly, statins that are effective at lowering cholesterol in humans do not necessarily do so in the established ApoE−/− and LDLR−/− mouse models. Therefore, if the early studies of statins had used only mouse models, we may have had to wait years before this blockbuster drug was discovered.

Now, 30 years after Lipitor, we're still waiting for the next equally successful blockbuster drug to further reduce the risks of CVD, which is the No. 1 cause of death in the United States.

Our researchers and many others are concerned that relying primarily on mouse models whose hearts differ greatly from humans’ may have impeded the discovery process. Therefore, we advocate for the use of rabbit models and/or other more relevant models for translational studies.