“It is a very strange disease,” says 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.’
Other times his face swelled, or he suddenly developed swollen knees, feet or hands, “so swollen that you can hardly bend your fingers.” And then there was that time when the swelling came up in his throat. Terrifying, literally. “That time I was really afraid of choking.”
About the author
Maarten Keulemans is science editor at de Volkskrant, specializing in microlife, climate, archeology and genetic engineering. He was named journalist of the year for his corona reporting.
Picavet turned out to have a rare genetic abnormality, which can cause him to suffer from swelling at unpredictable times. His body does not produce a certain blood protein properly, which means that the swelling system is turned on too much. The condition is called ‘hereditary angioedema’, or HAE for short. About 750 Dutch people, including Picavet’s sister, daughter and nephew, have it. Fortunately, the disease can also be mild.
Until that day, more than a year ago, that Picavet received an infusion at the Amsterdam UMC, containing a new treatment that corrects the gene defect. “I had just turned 50 for two weeks, this was the best birthday present I could wish for,” he says. Because although the disease, once diagnosed, in Picavet’s case could still be controlled reasonably with hormones, he has now come off the medication. “And I haven’t had any more attacks.”
Picavet is one of the two Dutch people who featured in a scientific report in the leading medical journal on Thursday New England Journal of Medicine, and the first Dutch person ever to be treated with the new genetic precision technique ‘crispr-cas’. A technique that cuts DNA in a targeted manner, at the place where it is desired. With previous gene therapy, this was always just a gamble, with the result that the therapy often did not work, and sometimes even induced cancer.
But now it’s different. In ten HAE patients who underwent the new gene therapy, attacks of swelling decreased by 95 percent. And that is putting it conservatively: four months after the infusion, the only swelling that the ten reported was a big thumb in a patient who had been kicked during sports. There are virtually no side effects, although the patients are followed for years.
‘It’s incredible,’ says internist and researcher Danny Cohn (Amsterdam UMC). ‘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 could functionally cure them.’ He talks about the suffering of patients like Picavet: constant swelling attacks, always that fear somewhere that an attack could be fatal. ‘I am touched every day by the motivations of these patients. The attacks often occur at stressful times. So many happy moments such as school parties, birthdays or weddings are ruined by this. And now this. It is incomprehensible. Goosebumps.’
‘What a beautiful story,’ says Rob Hoeben, professor of gene transfer at the LUMC, after viewing the results. ‘It seems safe and it seems to work, which makes me very enthusiastic.’ What is special, says Hoeben, is that the therapy does not so much tackle the broken gene itself, but another gene that still stops the swelling in a roundabout way. ‘That approach is new and courageous, and is now paying off.’ And it leaves you wanting more: there are probably more hereditary diseases that can be remedied via such a genetic back door, Hoeben thinks.
The treatment is therefore indicative of the medical revolution that is coming, Hoeben believes. Especially if crispr-cas will soon receive reinforcement from an even more precise gene therapy called ‘prime editing’, which can actually repair genetic defects in the body, instead of just cutting them in half. ‘If that works, it will go terribly fast. I then expect a flood of new applications.’
And new headaches, Hoeben adds. Because the pharmaceutical industry realizes all too well that miracle cures may come with a price tag. “People can easily charge a few million euros for such an infusion,” says Hoeben. ‘Who’s going to pay for that?’
Picavet, who has been following the science surrounding Crispr-Cas for years, is particularly impressed. Four hours on the drip, and the disease with which he seemed to be saddled for life is gone. A little elevation is the only side effect he got. “And to think that it was only ten years ago that Crispr-Cas was discovered,” he says. ‘This happened incredibly quickly.’