CRISPR gene therapy shows promise in treating severe inflammatory conditions

Nine people with a rare genetic disease that causes a life-threatening inflammatory response appear to have been cured after taking part in the first trial of a new version of CRISPR-based gene therapy.

This condition, called hereditary angioedema, causes sudden swelling of tissue that affects parts of the body such as the face and throat, similar to aspects of an allergic reaction, but cannot be treated with anti-allergy drugs.

Ten people who received a one-time gene therapy administered directly into the body saw a 95 per cent reduction in the number of 'swelling attacks' in the first six months after the treatment took effect. . Since then, all but one have had no further seizures for at least a year, although one patient who received the lowest dose had one mild seizure. “This is potentially a cure,” he says Padmalal Gurugama At Cambridge University Hospital in the UK, we worked on a new approach.

Hereditary angioedema is usually caused by mutations in the gene that encodes a protein called C1 inhibitor, which is involved in suppressing inflammation, which is part of the immune response.

People with this condition may experience a sudden buildup of fluid under their skin several times a month, which is painful and can cause suffocation if it gets stuck in the throat. This attack can be caused by a virus, changes in hormone levels, or stress.

Existing drugs that can reverse attacks work by blocking another molecule involved in inflammation called kallikrein, which is made in the liver. Because people can be born without the ability to make kallikrein without adverse effects, the results suggest that it is safe to permanently block kallikrein through gene therapy, Gurgama said.

The new treatment, developed by a company called Intellia Therapeutics in Cambridge, Massachusetts, consists of genetic material designed to cut the kallikrein gene. It is encapsulated in lipid nanoparticles and taken up by liver cells. One person was treated in the UK and nine in New Zealand and the Netherlands.

An unusual feature of this therapy is that it is administered directly to humans, a method also referred to as “in vivo” delivery. “They get one infusion and that's it,” he says. julian gilmore from University College London was not involved in the study. “It's very appealing.”

So far, most other CRISPR-based gene therapies have been administered “outside the body.” This means a more complex and time-consuming procedure of taking some of a person's cells outside the body, changing the cells in a lab, and then reinjecting them.

CRISPR gene therapy is being developed for multiple genetic diseases, with the first treatments recently approved in the UK and US to help patients with two forms of genetic anemia: sickle cell disease and beta-thalassemia. Ta.

The success of the latest trial is “very exciting,” Gilmore said. Development of CRISPR-based treatments for people with various liver-related conditions, called transthyretin amyloidosis. “This technology could be applied to any disease caused by a mutant protein produced exclusively in the liver, where it is desirable to knock down that protein,” he says.