CRISPR-based therapy shown to be safe, effective for people with transthyretin amyloidosis

A new type of therapy that ‘edits’ a gene in patients with a rare heart condition has been shown to be safe and effective, according to research from UCL and the Royal Free Hospital.

Results for the Phase I clinical trial, published in the New England Journal of Medicine, bring hope for people with transthyretin amyloidosis (ATTR), who have a build-up of misfolded transthyretin protein (known as amyloid) in their hearts that causes symptoms of heart failure.

Most of the treatment options currently available to patients involve managing the symptoms and slowing down the progression of the disease. As well as breathlessness and fatigue, the disease often causes numbness in the hands and can lead to patients feeling dizzy or collapsing. As the condition gets progressively worse, it leads to immobility and is ultimately fatal.

The new therapy, which uses the Nobel Prize-winning CRISPR-Cas9 gene editing technology, works by inactivating a gene in the liver that is responsible for production of transthyretin, resulting in the production of only negligible quantities of transthyretin.

In the trial the therapy was given to 36 patients via a one-off intravenous infusion. Results showed that it is safe in the short to medium term and initial evidence of the treatment’s efficacy were promising.

Of the patients who received the treatment, many of who 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 at follow-up 12 months later.

This is really promising news for people with this awful condition. 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.”

Professor Marianna Fontana, lead author of the study from UCL Division of Medicine and the National Amyloidosis Centre at the Royal Free Hospital

Professor Julian Gillmore, senior author of the study from UCL Division of Medicine and the National Amyloidosis Centre at the Royal Free Hospital, 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 III clinical 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.