Enter Crispr. Gillmore is the lead investigator of the first ever gene-editing clinical trial in human patients with ATTR amyloidosis—and it is one of the first times Crispr has been used to edit a gene directly inside the body. The trial is not only to demonstrate that gene editing can be safe, but that it can potentially cure devastating diseases by simply correcting a typo.
Paddy Doherty, who has strong roots in Gweedore in County Donegal, was the fifth person in the trial to receive the infusion. Paddy’s own father died from the condition in his sixties, although at the time it was put down to angina. It wasn’t until a cousin living in England got in touch and asked to come over and talk to the family that Paddy learned that it was more likely his father died from something he had never heard of—ATTR amyloidosis.
The drug, called NTLA-2001, works by inactivating the TTR gene and stopping the genetic expression of TTR in liver cells. It contains a protein that functions as a pair of molecular scissors, as well as an RNA molecule, analogous to a GPS, that guides the scissors to the faulty gene. When the scissors arrive they cut into the gene, turning it off and stopping the production of the TTR protein.
All six patients in the trial, which included Paddy, had hereditary ATTR amyloidosis, with polyneuropathy as their major suite of symptoms. The results were reportedin June 2021. While the trial was just a Phase I, which primarily just tests for safety, it was found to lower levels of TTR by an astonishing 90 percent after 28 days. And this reduction was found to last four to six months after the initial injection.