Novel gene-editing therapies offer hope for patients with thyroxine amyloid cardiomyopathy

A single intravenous infusion of NTLA-2001, a novel CRISPR/cas9-based gene-editing therapy, significantly reduces circulating transthyretine (TTR) protein levels in patients with ATTR amyloid cardiomyopathy, a progressive and fatal cause
of heart failure, according to the latest research presented today at the American Heart Association's 2022 Scientific Meeting.
Held in Chicago on November 5-7, 2022 and conducted online, the conference is an important global exchange
for updates on the latest scientific advances, research, and evidence-based clinical practice in cardiovascular science.

Transthyroxine is a protein produced by the liver that transports retinol (also known as vitamin A) and the thyroid hormone thyroxine into the
systemic circulation.
Transthyretine amyloidosis (ATTR) is caused
by the accumulation of fibers made up of misfolded transthyretin in organs, including the heart.
Fibers disrupt normal organ function, leading to progressive organ failure
.

"Although TTR protein stabilizers are available as a treatment option for patients with ATTR amyloidosis, it remains a progressive, universally fatal disease," said Julian D.
Gillmore, M.
D.
, a professor at the Amyloidosis Centre at University College London and lead author of the study
.
”

The researchers evaluated the safety, tolerability and efficacy of NTLA-2001, which precisely eliminates the TTR gene
in the liver of patients with amyloid cardiomyopathy with ATTR.
The purpose of a single intravenous injection of ntara-2001 is to minimize the production
of abnormal TTR protein.

The study included 12 patients with ATTR amyloidosis and patients
with varying degrees of heart failure requiring treatment.
The patient received a single NTARA-2001 infusion
.
The concentration level of the TTR protein in the bloodstream was measured at the beginning of the study and measured every 2, 4, and 6 months after a single intravenous dose of NTLA-2001
.

It was found that 28 days after a single intravenous injection of NTLA-2001, all patients experienced a rapid and profound reduction in circulating serum TTR protein by at least 90%.

These benefits continued until the last study visit
conducted 4 to 6 months after receiving the therapeutic infusion.
In addition, NTARA-2001 was generally well tolerated (meaning that only one serious adverse event was resolved), and most adverse events, such as infusion-related reactions, were minor
.

Gillmore said the main limitation of the study's interpretation is that it was an original phase 1 dose-escalation study
conducted in patients with amyloid cardiomyopathy with ATTR.

"This is the first human trial of gene editing in vivo or in vivo, and our study demonstrates that gene editing in humans is possible and safe
in the short term.
" We were impressed by the significant and sustained decline in patients' serum TTR protein levels," Gillmore said
.
"These results suggest that intravenous NTLA-2001 is a potential new treatment option that may halt disease progression or even lead to improvements
in patients with amyloid cardiomyopathy with ATTR.
" However, further research is needed to determine the long-term safety of NTLA-2001 and to continue monitoring and evaluating the potential impact
of significantly reduced TTR levels on clinical outcomes in patients.
”