MedicalResearch.com Interview with:
Luca A. Lotta, MD, PhD
Senior Clinical Investigator
MRC Epidemiology Unit
University of Cambridge
MedicalResearch.com: What is the background for this study? What are the main findings?
- Drugs that enhance the breakdown of circulating triglycerides by activating lipoprotein lipase (LPL) are in pre-clinical or early-clinical development.
- It is not known if these drugs will reduce heart attacks or diabetes risk when added to the current first line therapies (statins and other cholesterol-lowering agents).
- Studying this would require large randomised controlled trials, which are expensive (millions of GBPs) and time-consuming (years).
- Human genetic data can be used to provide supportive evidence of whether this therapy is likely to be effective by “simulating” a randomised controlled trial.
- Our study used naturally occurring genetic variants in the general population (study of ~400,000 people) to address this.
- Individuals with naturally-lower cholesterol due to their genetic makeup were used as model for cholesterol-lowering therapies (eg. Statins).
- Individuals with naturally-lower triglycerides due to genetic variants in the LPL gene were used as model for these new triglyceride-lowering therapies.
- We studied the risk of heart attacks and type 2 diabetes in people in different groups.
MedicalResearch.com: What should readers take away from your report?
Response: People with both naturally-lower triglycerides due to LPL gene variants and naturally-lower cholesterol due to their genetic makeup at other genes had lower risk of heart attacks and diabetes than people with just naturally-lower cholesterol.
This suggests that adding LPL enhancing agents to statins is likely to result in further lower risk of heart disease but also lower risk for diabetes, suggesting that this combination therapy could be more effective while also being safer (with regards to diabetes risk).
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: This research has the potential to support and inform future efforts to study these emerging drugs in large human trials.
MedicalResearch.com: Is there anything else you would like to add?
Response: Human genetics is increasingly used to inform the identification and validation of drug targets.
Lotta LA, Stewart ID, Sharp SJ, et al. Association of Genetically Enhanced Lipoprotein Lipase–Mediated Lipolysis and Low-Density Lipoprotein Cholesterol–Lowering Alleles With Risk of Coronary Disease and Type 2 Diabetes. JAMA Cardiol. Published online September 19, 2018. doi:10.1001/jamacardio.2018.2866
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