A groundbreaking gene therapy is being hailed as a ‘medical magic wand’ after the treatment transformed the lives of patients with a hereditary condition that causes painful and potentially fatal swelling.
Patients who participated in the first human trial of the therapy experienced dramatic improvement in their symptoms, and many were able to come off the long-term medication and return to their normal lives.
Dr. Hilary Longhurst, the lead researcher at Te Toka Tumai Hospital in Auckland City, said the single-dose therapy appeared to provide a permanent cure for her patients’ “highly debilitating symptoms”.
Hereditary angioedema, or HAE, is a rare disease that affects about one in 50,000 people. It is caused by a genetic mutation that causes patients to develop leaky blood vessels. This causes irregular swellings that usually affect the lips, mouth, throat, intestines, hands and feet.
Attacks occur as often as twice a week and last hours to days. People can become bedridden as the swelling affects the intestines, and the disfiguring effect on the face can prevent people from leaving the house. The most severe flare-ups affect the throat and can lead to choking and death.
Cleveland, a 54-year-old from Suffolk who took part in the trial, has been seizure-free since receiving the therapy 18 months ago. “I have experienced a radical improvement in my physical and mental well-being,” he said. “The randomness, unpredictability and potential severity of the attacks have made it almost impossible to live my life. All my life I constantly wondered if my next attack would be serious.
“The swellings are painful and disfiguring. I was ashamed to go outside in case of an attack. I have been admitted to hospital with swelling in my neck and throat that has affected my ability to breathe.”
Judy Knox, a nurse from New Zealand who also took part in the trial, said the therapy was “like a medical magic wand”. Before her diagnosis, she experienced abdominal swelling with vomiting and severe pain that lasted for days. Dental work caused dangerous swelling in her mouth, causing her to suffocate. “It changed my life,” she said.
Knox previously treated the condition with androgen medications, but supplies were not always reliable. She is now off the medication and feels like she has a “whole new life”.
HAE is caused by a mutation in the C1 inhibitor gene. When the gene stops working, people produce a protein called kallikrein. This stimulates the build-up of another protein, bradykinin, which is responsible for leaky blood vessels and swelling.
Ten patients took part in the small phase one trial in Britain, New Zealand and the Netherlands. They were all given an infusion of ‘nanolipids’, designed using Crispr, a Nobel Prize-winning gene-editing tool, to enter liver cells and switch off the kallikrein gene. The therapy prevents the body from overproducing bradykinin, with dramatic consequences for patients.
“It’s changing patients’ lives,” says Dr Padmalal Gurugama, consultant in clinical immunology and allergy at Cambridge University Hospital. “My patient had seizures every three weeks and that gentleman has had no seizures in the last 18 months. He doesn’t take any medications. That is amazing.”
The results of the first patients are published in the New England Journal of Medicineand larger trials are underway. Doctors have treated another 25 patients in a phase two trial and hope to recruit people for a final phase three trial next year.
Despite the dramatic results, the therapy is not expected to be available anytime soon. Barring proving themselves in the remaining trials, such one-off gene therapies are among the most expensive treatments in the world, and far from a shoo-in for the NHS.
Prof. Paul Morgan, an immunologist at Cardiff University, called the results remarkable. “They demonstrate the potential to permanently cure HAE with a single treatment. Of course, larger clinical trials are now needed, covering the different types of HAE in different populations,” he said.
Recent trials have cost one-off gene therapies between $1 million and $2 million, meaning the treatments may only be affordable in wealthy countries, Morgan added. “Nevertheless, this study offers a real prospect of a cure for some HAE patients.”
Dr. Michael Tarzi, senior lecturer and honorary consultant at the Brighton and Sussex Medical School, was also impressed. “This is an excellent application of new technology, potentially providing curative treatment for patients with HAE,” he said.