I was briefly on statins several years ago, for six months. It made me very absent-minded; I never made it to the painful muscles stage. But I had always wondered about the functional of cholesterol in the blood. Michael Brooks finally tells me in NewScientist (11 February 2017):
A fatty biomolecule synthesised primarily in the liver, cholesterol forms cell walls and the myelin sheaths that protect neurons in the brain. It plays a part in biological processes from cell signalling to making vitamin D, and may even help fight infections.
So it has its uses. Michael Le Page, in the same issue of NewScientist, reports on a target for gene editing – basically, get a treatment and go off of statins forever:
In 2005, it was discovered that a few people naturally have very low cholesterol levels, thanks to mutations that prevent their livers from making a protein called PCSK9. “They have a lower incidence of cardiovascular disease and no apparent side effects whatsoever,” says Gilles Lambert at the University of Reunion Island, who studies PCSK9.
The PCSK9 protein normally circulates in the blood, where it degrades a protein found on the surface of blood vessels. This second protein removes LDL cholesterol from the blood: the faster it is degraded by PCSK9, the higher a person’s cholesterol levels. But people who lack PCSK9 due to genetic mutations have more of this LDL-removal protein, and therefore less cholesterol in their blood.
Drugs were developed to reduce PCSK9, but they turn out to be expensive and cumbersome to use.
But gene editing provides a radical alternative. Using the CRISPR technique, the team at AstraZeneca have disabled human versions of the PCSK9 gene in mice.
They did this by injecting the CRISPR Cas 9 protein and a guiding RNA sequence into the animals. The RNA guide helps the Cas9 protein bind to a specific site in the gene. It then cuts the gene at that point, and when the break is repaired, errors that disable the gene are likely to be introduced.
There was an even bigger fall in cholesterol levels in the mice given the CRISPR treatment than in those injected with the antibody drugs.
They still see human trials starting in about a decade.
