A CRISPR Therapy for Heart Disease May Be on the Way

CRISPR Base Editing Depletes LDL Cholesterol and Lipoproteins

Verve therapeutics have announced new data at the ISSCR 2020 Virtual Annual Meeting. The researchers have successfully used adenine base editing in monkeys to reduce LDL cholesterol and lipoproteins rich in triglycerides. In one study, 7 monkeys were given a single infusion of CRISPR to turn off the ANGPTL3 gene, and in another study, 7 monkeys were treated with CRISPR to switch off the PCSK9 gene. The ANGPTL3 gene product enhances the levels of lipoproteins in the blood, and the PCSK9 gene product enhances levels of LDL cholesterol and ANGPTL3 in the blood. Therefore, these genes have been targeted because they increase the levels of LDL cholesterol and lipoproteins, which commonly leads to the build-up of plaque and then coronary heart disease.

When the researchers switched off the ANGPTL3 gene, there was a 95% reduction in ANGPTL3, and this caused a 64% decrease in the levels of triglycerides. Furthermore, when the PCSK9 gene was switched off, the PCSK9 levels had decreased by 89% and subsequently the LDL cholesterol levels had decreased by 59%. Therefore, the CRISPR base editing altered the genes that promote cholesterol levels and thus could serve as a cardioprotective therapy.

“These proof-of-concept data, which to the best of our knowledge represent the first successful application of the base editing technology in non-human primates, show that we can safely edit the primate genome at highly efficacious levels to significantly lower blood LDL cholesterol and triglycerides. The findings are very encouraging and add to our growing body of evidence in using both base editing and CRISPR-Cas9 in vivo against various gene targets. We expect to choose a lead program by year-end 2020 with the goal of initiating human clinical studies within the next three years.” said Sekar Kathiresan, M.D., co-founder and chief executive officer of Verve Therapeutics.

Reference: https://www.vervetx.com/press-releases/verve-therapeutics-presents-new-data-in-non-human-primates-validating-gene-editing-as-a-treatment-approach-for-coronary-heart-disease-at-the-isscr-2020-virtual-annual-meeting/