In the first human trial, a single-dose treatment has transformed the lives of patients suffering from a potentially deadly condition
A new gene therapy has been hailed as a “medical magic wand” for patients with hereditary angioedema (HAE), a rare genetic disorder that causes painful and potentially fatal swelling. The first human trial of this therapy was conducted, and the results were very promising. Patients experienced a significant improvement in their symptoms, and many of them were able to stop taking long-term medication and return to their normal lives. The principal investigator of the trial, Dr. Hilary Longhurst, believes that the single-dose therapy could provide a permanent cure for her patients’ “very disabling symptoms.”
HAE affects approximately one in 50,000 people and is caused by a genetic mutation that results in leaky blood vessels. The disease produces unpredictable bouts of swelling that can affect different parts of the body such as the lips, mouth, throat, bowels, hands, and feet. Some patients experience attacks twice a week that can last for hours or days. Severe attacks can lead to bedridden patients, disfigurement of the face, suffocation, and death.
Cleveland, a 54-year-old participant from Suffolk in the trial, has been attack-free for 18 months since receiving the therapy. “I’ve had a radical improvement in my physical and mental wellbeing,” he said.
Judy Knox, a nurse in New Zealand who also took part in the trial, said the therapy was “like a medical magic wand”. Before her diagnosis, she suffered abdominal swelling with vomiting and severe pain that lasted for days. Dental work prompted dangerous swelling in her mouth, which threatened to suffocate her. “It’s changed my life,” she said.
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Knox used to manage her condition with androgen medication, but due to unreliable supplies, she has stopped taking it. She now feels that she has a whole new life. Her condition, known as HAE, is caused by a mutation in the C1 inhibitor gene. When the gene is not functioning properly, the body produces an excess of a protein called kallikrein. This leads to the accumulation of another protein called bradykinin, which is responsible for the swelling and leaky blood vessels. In a small phase-one trial conducted in the UK, New Zealand, and the Netherlands, ten patients were given nanolipids infused with Crispr, a gene-editing tool that won the Nobel prize. The nanolipids were designed to enter liver cells and knock out the kallikrein gene. The treatment successfully prevented the body from overproducing bradykinin, resulting in significant improvements for the patients.
“It’s transforming patients’ lives,” said Dr Padmalal Gurugama, a consultant in clinical immunology and allergy at Cambridge University hospital. “My patient was having attacks every three weeks and that gentleman has not had any attacks in the past 18 months. He is not taking any medications. That is amazing.”
The first patient results for a new medical treatment have been published in the New England Journal of Medicine. The doctors have treated 25 more patients in a phase-two trial and plan to recruit for a final phase-three trial next year. Although the initial results were promising, the therapy is not expected to be available anytime soon. It needs to prove its effectiveness in remaining trials. Also, one-shot gene therapies are among the most expensive treatments globally and are not guaranteed to be available under 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, encompassing the different types of HAE in different populations, are now needed,” he said.
Recent reviews had costed one-shot gene therapies at between $1m (£790,000) and $2m, meaning the treatments might only be affordable in wealthy countries, Morgan added. “Nevertheless, this study offers the real prospect of cure for some HAE sufferers.”
Dr Michael Tarzi, a senior lecturer and honorary consultant at Brighton and Sussex Medical School, was similarly impressed. “This is an outstanding application of new technology, which potentially offers a curative treatment to patients with HAE,” he said.