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The therapy, which uses the Nobel Prize-winning CRISPR/Cas9 technology, works by inactivating a gene in the liver which is responsible for production of a protein called transthyretin.
People with transthyretin (ATTR) amyloidosis have a build up of misfolded transthyretin protein (known as amyloid) in their hearts which causes symptoms of heart failure.
As well as breathlessness and fatigue (heart failure symptoms) the disease often causes numbness in the hands and can lead to patients feeling dizzy or to collapse. As the condition gets progressively worse, it leads to immobility and is ultimately fatal.
Most of the treatment options currently available to patients involve managing the symptoms and slowing down the progression of the disease.
Patients on the trial received the CRISPR/Cas9-based ‘gene editing’ therapy via a one-off intravenous infusion. The molecule inactivates the transthyretin gene within liver cells resulting in production of only negligible quantities of the transthyretin protein.
The phase 1 study of the CRISPR/Cas9 treatment showed that it is safe in the short to medium term and, furthermore, revealed promising results in terms of its efficacy.
Of the 36 patients who received the treatment, many of whom had advanced symptoms of heart failure at the beginning of the study, the vast majority reported that their condition had stopped getting worse or had improved 12 months later.
Lead author of the study, Professor Marianna Fontana from the National Amyloidosis Centre at the Royal Free Hospital and UCL Division of Medicine, said she was thrilled with the results. “It’s really promising news for people with this awful condition,” she said.
“The hope is that, in patients diagnosed in the early stage of the disease, this treatment will offer the prospect of preserving a good quality of life without the need for ongoing therapy.”
Senior author, Professor Julian Gillmore from the National Amyloidosis Centre at the Royal Free Hospital and UCL Division of Medicine, said: “This trial establishes for the first time that a gene can be selectively, safely and permanently inactivated in the human body which is an exciting prospect for treatment and possibly even prevention of a range of diseases in the future.’’
Professors Fontana and Gillmore are currently running a global phase 3 trial involving more than 700 patients, the results of which will firmly establish whether the treatment is effective.
The investigational therapy, designated nexiguran ziclumeran (nex-z), is being developed by U.S.-based biotechnology company Intellia Therapeutics, Inc.
Image: Prof Marianna Fontana.
