Northland patient with rare disorder cheers success of gene-editing treatment

Being “a guinea pig” in a world trial of a breakthrough gene-editing treatment was a great decision for a Northland patient suffering from a rare disorder.

Whangārei nurse Judy Knox has hereditary angioedema, which causes severe and unpredictable swelling attacks that are potentially fatal if they restrict one’s airways.

The disorder affects one in every 50,000 people; however, as it is rare, it is often incorrectly diagnosed.

Knox, a practice nurse in her 70s, said the disorder has affected a number of her family members but it was not known about until the 1980s.

“We used to get very sick with abdominal pain - vomiting and sick as a dog. Then they would operate on it, open us up, because they just did not know what it was.”

Knox said dental surgery could prompt dangerous swelling in her mouth - including the tongue, palette and throat - that was excruciatingly painful and threatened to suffocate her.

Once she was diagnosed with hereditary angioedema, she was able to carefully manage her symptoms with androgen medication, but its supply was not always reliable and emergency medications were extremely expensive.

After meeting other Kiwis with the disorder at a conference, Knox also became concerned for those who were more severely impacted and not able to manage their symptoms.

So, when the opportunity came up to take part in an international study for a gene-editing therapy called Crispr/Cas9, she put her hand up to be one of the first people in the world to receive the therapy.

“To some extent it could’ve been risky, but at my stage - I’m in my early 70s - I’m prepared to take that risk because I’ve had a great life and I’m prepared to help people,” she said.

The small study was successfully run by researchers from the University of Auckland, Amsterdam University Medical Center and Cambridge University Hospitals, with interim results just published in a leading journal.

New Zealand was chosen to lead the research as, at that time in late 2021, it had relatively fewer Covid-19 cases than other countries.

Knox had her Crispr/Cas9 treatment - a one-off intravenous treatment - in August 2022, and it was so successful she was able to come off her medication.

“I’m effectively cured - I don’t have to take my medication at all,” she said. “It’s changed my life.”

Not only is Crispr/Cas9 proving effective in treating hereditary angioedema, people can get excited at the prospect of similar treatments curing other genetic disorders, Knox said.

“It’s incredible - it’s just so encouraging for people who have got diseases that cause them terrible difficulties throughout their lives.

“People have to be excited about the future that medical science has because it’s just amazing.”

Gene-editing therapy safe and effective, trial finds

The patients involved in the trial have had their lives transformed, said principal investigator Dr Hilary Longhurst, an Auckland clinical immunologist and honorary associate professor at the University of Auckland.

“It looks as if the single-dose treatment will provide a permanent cure for my hereditary angioedema patients’ very disabling symptoms,” she said.

Results of the phase-one trial for Crispr/Cas9 have just been published in the New England Journal of Medicine.

The trial of more than 10 patients from New Zealand, the Netherlands and the UK found there were no serious or lasting side-effects from the single infusion, and a reduction of almost all (95 per cent) of swelling attacks.

The patients will be followed for a further 15 years to continue to assess long-term safety and efficacy.

Longhurst said there is also huge potential for the development of similar treatments for other genetic disorders.

Now, a larger and more robust, placebo-controlled phase-two trial of Crispr/Cas9 is under way, and a pivotal phase-three trial is planned to start in the second half of 2024.

The studies have been funded by US company Intellia Therapeutics.

The therapy affects only the patient and is not passed on to their children, who still have a 50/50 chance of inheriting the disorder.

Denise Piper is a news reporter for the Northern Advocate, focusing on health and business. She has more than 20 years in journalism and is passionate about covering stories that make a difference.