A single treatment with a groundbreaking gene-editing therapy transformed the lives of a group of patients suffering from an inherited disease, according to the lead researcher.
Patients in New Zealand, the Netherlands and the United Kingdom have hereditary angioedema, a genetic disease that causes attacks of severe, painful and sudden swelling. These interfere with normal activities and have the potential to cause airway damage and death.
Researchers from the University of Auckland, Amsterdam University Medical Center and Cambridge University Hospital have successfully treated more than ten patients with CRISPR/Cas9 technology, with preliminary findings recently published in a leading journal.
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“It looks like this single-dose treatment will provide a permanent cure for the very disabling symptoms of my hereditary angioedema patients,” said lead investigator Dr. Hilary Longhurst, clinical immunologist at Auckland Hospital Te Toku Tumai and honorary Both are associate professors. At the University of Auckland.
“Also, of course, there is huge potential for the development of similar CRISPR/Cas9 treatments for other genetic disorders.”
Globally, it is estimated that one in 50,000 people have hereditary angioedema, however, because it is rare, it is often not correctly diagnosed.
In the phase one study, there were no serious or lasting side effects from the single infusion, which took place over two to four hours, under clinical supervision through late 2021 and beyond.
The investigational therapy, called NTLA-2002, uses in vivo CRISPR/Cas9 technology to target the KLKB1 gene, which is responsible for the production of plasma prekallikrein.
By editing this gene, the therapy reduces total plasma kallikrein levels, effectively preventing attacks of angioedema (swelling).
The trial published in the New England Journal of Medicine demonstrated a dose-dependent reduction in total plasma kallikrein protein, with reductions of up to 95 percent achieved.
An average reduction of 95 percent in angioedema attacks was seen in all patients through the latest follow-up.
Patients in the initial study will be followed for the next 15 years to continue assessing long-term safety and efficacy. A larger and more robust, double-blind, placebo-controlled phase two trial is underway and a phase 3 trial is underway. Planned to launch in the second half of 2024.
Dr. Danny Cohn of the Department of Vascular Medicine at Amsterdam University Medical Center says these promising results are a step forward for this group of patients.
“We have never been closer to the ultimate treatment goal of normalizing the lives of hereditary angioedema patients and providing complete control of the disease,” said Dr. Cohn.
Dr. Padmalal Gurugama, consultant in clinical immunology and allergy at Cambridge University Hospitals, UK, says that gene editing therapy has the potential to significantly improve the lives of patients.
“Hereditary angioedema can cause patients to have severe swelling and intense pain that can be life-threatening as well as restrict normal activities such as going to work or school.
“Because it is often misdiagnosed, many patients undergo unnecessary treatments and invasive procedures.” The therapy only affects the patient and is not given to their children, who still have the possibility of inheriting the disorder.
The study is funded by US company Intellia Therapeutics, which chose New Zealand to lead the research because, at the time – late 2021, it had relatively few COVID-19 cases compared to other countries.
So far, the only approved CRISPR therapy, CASGEVY, is for sickle cell disease and beta-thalassemia. However, CASGEVY is an ex vivo CRISPR therapy, where cells are taken from the patient and edited outside the body and then reused, while NTLA-2002 is an in vivo CRISPR therapy, where targeted gene editing is done directly into the body. Happens inside the body.
CRISPR technologies are being used to develop treatments for a wide variety of diseases, such as genetic disease, heart disease, cancer, and autoimmune diseases. Check out Intelia’s website.
Judy Knox, a patient from New Zealand, said, “Taking CRISPR/Cas9 therapy has been like a medical magic wand, it has changed my life.”
Before she was diagnosed, Judy would suffer from abdominal bloating with vomiting and severe pain that could last for several days. Dental surgery could have caused dangerous swelling of his mouth, including his tongue and palate, and his larynx, which was extremely painful and put him at risk of suffocation.
Once diagnosed Judy, who is a nurse in Whangarei, carefully managed her androgen medication and was prepared to increase it (within the prescribed dosage) to deal with any flare-ups.
In recent years the supply of this medicine was not always reliable which became a huge concern for him. Judy knew that there were emergency medicines available in New Zealand which, despite being funded, were still very expensive.
When the opportunity arose to participate in the study, she wasted no time in volunteering and was one of the first people in the world to receive CRISPR/Cas9 therapy at a clinical research center in New Zealand.
“I raised my hand and said, ‘I’ll do it.’ And because it was beneficial to others.”
Another factor was their concern about the continued availability of the medications they needed.
She has now weaned herself off the medicines and feels she has got a ‘whole new life’.
For anyone considering therapy, he said, “Go for it, because it works.”
