Nine people with a rare genetic condition that causes life-threatening inflammatory reactions appear to have been cured, after taking part in the first trial of a new version of a CRISPR-based gene therapy.
The condition, called hereditary angioedema, causes people to have sudden episodes of tissue swelling that affects body parts such as the face or throat, similar to aspects of an allergic reaction, although they can’t be treated with anti-allergy medicines.
Ten people who had the one-off gene treatment that is given directly into the body saw their number of “swelling attacks” fall by 95 per cent in the first six months as the therapy took effect. Since then, all but one have had no further episodes for at least a further year, while one person who had the lowest dose of the treatment had one mild attack. “This is potentially a cure,” says Padmalal Gurugama at Cambridge University Hospitals in the UK, who worked on the new approach.
Hereditary angioedema is caused by mutations in a gene that encodes a protein called C1-inhibitor, which is normally involved in damping down inflammation, part of the immune response.
People with the condition may have sudden episodes of fluid accumulation under their skin several times a month, which are painful and can suffocate them if their throat becomes blocked. The attacks can be triggered by viruses, changing hormone levels or stress.
Existing medications that can reverse the attacks work by blocking a different molecule involved in inflammation, called kallikrein, made by the liver. People can be born without any ability to make kallikrein with no ill effects, which suggested that permanently blocking it via gene therapy would be safe, says Gurugama.
The new therapy, made by a firm called Intellia Therapeutics in Cambridge, Massachusetts, consists of genetic material designed to make cuts in the kallikrein gene. It is encapsulated in lipid nanoparticles, which liver cells take up. The treatment was given to one person in the UK and nine others in New Zealand and the Netherlands.
The unusual feature of this treatment is that it was administered directly into people, a method sometimes called “in vivo” delivery. “They go in for one infusion and it’s job done,” says Julian Gillmore at University College London, who wasn’t involved in the study. “It’s hugely attractive.”
Most other CRISPR-based gene therapies so far have been administered “ex vivo”, which means taking some of the person’s cells out of their body, changing them in the lab and then reinfusing them, a more complicated and lengthy procedure.
CRISPR gene therapies are being developed for multiple genetic conditions, with the first such treatment recently being approved in the UK and US to help people with sickle cell disease and beta-thalassaemia, two forms of inherited anaemia.
The success of the latest trial is “pretty exciting”, says Gillmore, who is developing a CRISPR-based therapy for people with a different condition involving the liver, called transthyretin amyloidosis. “Any disease that’s caused by a mutated protein that’s exclusively produced in the liver, where knocking down that protein is a good thing to do, would potentially be amenable to this technique,” he says.