A US start-up has successfully treated the first patients using a Crispr gene-editing therapy directed inside the body to an internal organ.
The early trial data from Intellia Therapeutics, co-founded by Nobel Prize winner Jennifer Doudna, marked a breakthrough for Crispr-based treatments, showing scientists had overcome challenges that had previously restricted the technology’s use to editing cells outside the body or in the eye.
The Boston-based start-up, working with biotech company Regeneron, treated transthyretin amyloidosis, a devastating disease in which a build-up of a problematic protein hits a patient’s heart and nervous system, cutting their life expectancy.
John Leonard, Intellia’s chief executive, said he was “super gratified” to see the positive results, which opened the door to treatments beyond the “tiny subset” of diseases for which Crispr-based treatments have been trialled.
“The allure and the promise of Crispr is this notion that you can change any gene, anyhow, anywhere in the genome, so long as you can get it there. And that last proviso is the key one,” he said. “This is the first time Crispr has ever been infused into a patient . . . and the first time we’ve been able to target a gene successfully.”
Crispr — which stands for clustered regularly interspaced short palindromic repeats — is a system used by bacteria to protect themselves against viruses. In 2012, Doudna and her French colleague Emmanuelle Charpentier discovered how to use it as a gene-editing tool.
Shares in Intellia have risen 233 per cent since it went public in 2016. The company is one of three with the original patents from the discoveries. The others are Crispr Therapeutics, which treated patients for sickle cell disease, and Editas Medicine, which is in trials to treat a form of inherited blindness.
Intellia is looking to edit bone marrow to treat blood-based diseases without transplanting cells, including working with the Bill & Melinda Gates Foundation to treat patients in Africa with sickle cell disease.
In its phase 1 trial, a Crispr treatment was inserted in a lipid nanoparticle, which was picked up in the blood by the same tissue that grabs cholesterol globules, and transported to the liver. There, the one-off treatment inactivated the TTR gene and reduced the problematic protein 87 per cent in patients on the highest dose. There were no serious side effects by day 28.
Julian Gillmore, a professor of medicine at University College London who was the chief investigator on the phase 1 trial, has treated ting patients with the type of amyloidosis for 25 years, but for two decades there was little he could do for them. In the past five years, he has been able to use gene silencers — but those treatments appeared to be less effective and required regular infusions.
“From my own personal perspective, to have watched these patients get worse for so many years, I’ve known families for years totally decimated by this disease, it is incredible to see this revolution,” he said.