2 Dutch among 10 "functionally cured" of hereditary swelling disease by new gene therapy

A new experimental gene therapy has functionally cured ten patients, including two Dutch, from the swelling disease 'hereditary angioedema,' or HAE for short. Treatment with the new precision genetic technique ‘crispr-cas’ reduced the ten HAE patients’ symptoms by 95 percent, according to the report published by researchers from Amsterdam UMC, among others, in the New England Journal of Medicine on Thursday.

HAE is a rare genetic abnormality that causes random attacks of swelling. The body does not produce a certain type of blood protein properly, which means that the swelling system is overactive. About 750 Dutch people have HAE in various severity.

In the ten HAE patients who underwent the new gene therapy a - which corrects the genetic defect by cutting DNA in a targeted manner - a year ago, attacks of swelling decreased by 95 percent. And that is a conservative number. Four months after the infusion, the only swelling reported was a swollen thumb in one patient who got injured during sports. The patients also reported virtually no side effects, though the researchers will continue to follow them.

The Volkskrant spoke to one of the two Dutch patients involved in the study - Charles Picavet, a 51-year-old elderly care worker from Amsterdam. “Especially after stress had disappeared, I would often suddenly have an attack with terrible stomach pain. Once every few weeks, I would spend a day in bed, deathly ill. And the next day, I was back to my old self.”

Sometimes, his face, knees, or hands would swell up - “So swollen that you can hardly bend your fingers.” And there was a time when his throat swelled shut. “That time, I was terrified of choking.”

And then a year ago, he received an infusion at the Amsterdam UMC containing the new treatment. “I had just turned 50 two weeks earlier. This was the best birthday present I could wish for,” he told the newspaper. Because since then, he hasn’t had a single attack, even though he stopped the hormones that kept it reasonably under control in the past.

“It’s incredible,” internist and researcher Danny Cohn of Amsterdam UMC told the Volkskrant. “I have been treating patients with HAE for seven years now, but I never dreamed that we would already be at the point where we can functionally cure them.” Because the attacks often follow stress and excitement, they ruin patients' happy moments like school parties, birthdays, or weddings. “And now this. It is incomprehensible. Goosebumps.”

Rob Hoeben, LUMC professor of gene transfer, called the results “beautiful” after reading the report. “It seems safe, and it seems to work. That makes me very enthusiastic.” He is impressed that the treatment doesn’t tackle the broken gene itself but another gene that stops the swelling in a roundabout way. “That approach is new and courageous and is now paying off.”

Hoeben thinks the new treatment can work on a host of other hereditary diseases and is indicative of a looming medical revolution. Especially if crispr-cas gets reinforcement from an even more precise gene therapy called prime editing, which repairs genetic defects instead of just cutting them in half. “If that works, it will go terribly fast. I then expect a flood of new applications.”