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A group of patients with an inherited disease had their lives transformed by a single treatment of a revolutionary gene-editing therapy, according to the lead researcher of a trial published in the New England Journal of Medicine.
Patients from New Zealand, the Netherlands and the United Kingdom suffer from hereditary angioedema, a genetic disorder characterized by severe, painful and unpredictable attacks of swelling. These interfere with daily life and can affect the respiratory tract and prove fatal.
Today, researchers from the University of Auckland, University of Amsterdam Medical Center and Cambridge University Hospitals have successfully treated more than 10 patients with CRISPR/Cas9 therapy, with interim results.
just published.
“It appears that the single-dose treatment will permanently cure the very debilitating symptoms of my patients with hereditary angioedema,” says lead researcher Dr. Hilary Longhurst, who is both a clinical immunologist at Te Hospital. Toku Tumai of Auckland and Honorary Associate. professor at the University of Auckland.
“Plus, of course, there is huge potential to develop similar CRISPR/Cas9 treatments for other genetic disorders.” Globally, an estimated 1 in 50,000 people suffer from hereditary angioedema. However, due to its rarity, it is often misdiagnosed.
In the phase I study, no serious or lasting side effects were observed following the single infusion, which took place over two to four hours under clinical monitoring starting in late 2021.
The investigational therapy, called NTLA-2002, uses CRISPR/Cas9 technology in vivo to target the KLKB1 gene, responsible for the production of plasma prekallikrein. By modifying this gene, the therapy reduces total plasma kallikrein levels, effectively preventing angioedema (swelling). ) attacks.
The trial demonstrated a dose-dependent reduction in total plasma kallikrein protein, with reductions up to 95%. An average reduction of 95% in angioedema attacks was observed in all patients until the last follow-up.
Patients in the initial study will be followed for an additional 15 years to continue to evaluate long-term safety and effectiveness. A larger, more robust, double-blind, placebo-controlled Phase II trial is underway and a Phase III trial is expected to start in the second half of 2024.
Dr Danny Cohn, from the Department of Vascular Medicine at the University Medical Center Amsterdam, says these promising results are a step forward for this group of patients.
“We have never been closer to the ultimate goal of treatment, which is to normalize the lives of patients with hereditary angioedema and provide total disease control,” says Dr. Cohn.
Dr Padmalal Gurugama, consultant in clinical immunology and allergy at Cambridge University Hospitals, UK, says gene editing therapy has the potential to significantly improve patients’ lives.
“Hereditary angioedema can cause patients to experience severe swelling and pain that can be life-threatening and 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 passed on to their children, who always have an equal chance of inheriting the disease.
So far, the only approved CRISPR therapy, CASGEVY, is for sickle cell disease and beta thalassemia. However, CASGEVY is an ex vivo CRISPR therapy, in which cells are taken from the patient and edited outside the body, then reinjected, while NTLA-2002 is an in vivo CRISPR therapy, in which targeted editing of genes occurs directly in the body.
CRISPR technologies are used to develop treatments for a wide range of diseases, such as genetic diseases, cardiovascular diseases, cancer and autoimmune diseases.
More information:
Hilary J. Longhurst et al, In vivo CRISPR-Cas9 gene editing of KLKB1 for hereditary angioedema, New England Journal of Medicine (2024). DOI: 10.1056/NEJMoa2309149
Provided by the University of Auckland
Quote: Gene editing offers hope for people with hereditary disorders (February 2, 2024) retrieved February 2, 2024 from
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