Singapore Leads Asia in Groundbreaking Gene Editing Trial for Rare Heart Disease
Key Insights
NUHCS (search) has become the first center in Asia to enroll patients in the MAGNITUDE trial, testing Nexiguran Ziclumeran (NTLA-2001), a single-dose gene editing therapy for transthyretin amyloid cardiomyopathy (search) (ATTR-CM (search)).
The innovative treatment aims to alter patients' DNA to reduce production of misfolded transthyretin (search) proteins that accumulate in the heart and other organs, potentially offering hope for the approximately 150 ATTR-CM (search) patients in Singapore.
Early phase clinical trials have shown promising results with "consistent, rapid, and durable reductions" in the abnormal protein causing ATTR-CM (search), with minimal side effects reported thus far.
The National University Heart Centre, Singapore (search) (NUHCS (search)) has achieved a significant milestone by becoming the first medical center in Asia to recruit patients for an international gene editing clinical trial targeting transthyretin amyloid cardiomyopathy (search) (ATTR-CM (search)), a rare and potentially fatal heart disease.
The MAGNITUDE study is investigating Nexiguran Ziclumeran (nex-z, also known as NTLA-2001), a revolutionary single-dose gene editing therapy administered intravenously. The treatment is designed to alter patients' DNA to slow down the production of abnormal transthyretin (search) proteins that cause the disease.
ATTR-CM (search) affects approximately 150 patients in Singapore and is characterized by the build-up of misfolded, deformed transthyretin (search) proteins in the heart, nerves, and other organs due to genetic mutation or aging. The condition can lead to heart failure (search) if not diagnosed and treated promptly.
Patient Experience Highlights Disease Burden
Mr. Chua Ah Hai, a 62-year-old Singaporean, exemplifies the devastating progression of ATTR-CM (search). Diagnosed incidentally following a car accident ten years ago, Mr. Chua has experienced a significant decline in his quality of life despite years of medication.
"Over time, Mr. Chua's hands and legs became stiff, and the once active 62-year-old could no longer walk," reports indicate. His condition has necessitated frequent hospital visits due to heart failure (search) episodes and injuries from falls caused by nerve damage associated with the disease.
The lack of a curative treatment has left patients like Mr. Chua with limited options until now. Current symptoms of ATTR-CM (search) can include numbness in extremities, lethargy, and dizziness – vague manifestations that can complicate timely diagnosis.
First in Asia to Implement Groundbreaking Approach
Assistant Professor Lin Weiqin, Clinical Director of the Heart Failure (search) and Cardiomyopathy Programme at NUHCS (search), is leading the Singapore arm of this international trial. The double-blind study will evaluate the impact of the gene editing therapy on patients with ATTR-CM (search).
"Gene editing therapy has been approved in other countries, for use in some neuro-muscular conditions, cancers and inherited blood disorders. If this trial is successful, it will be the first DNA altering treatment used in the field of adult cardiology and offers new hope to patients living with ATTR-CM (search)," explained Asst Prof Lin, who is also a Senior Consultant at NUHCS (search).
The first patient in Asia was recruited in Singapore and received treatment in September 2024. Since then, four additional patients have joined the study, with Mr. Chua being the most recent participant. The gene editing therapy is being administered alongside standard ATTR-CM (search) treatments as part of the protocol.
Promising Early Results
While definitive outcomes from the MAGNITUDE study may take two to three years to materialize, early phase clinical trials have shown encouraging results. These include "consistent, rapid, and durable reductions" in the abnormal protein causing ATTR-CM (search), with minimal side effects reported.
Importantly, patients in Singapore who have received the treatment have not reported any adverse effects thus far, suggesting a potentially favorable safety profile.
Ongoing Recruitment
NUHCS (search) continues to recruit eligible patients for the trial. Participants must be between 18 and 90 years old, diagnosed with heart failure (search) due to ATTR, currently on medication for heart failure, and have experienced heart failure within the past year. Female participants are eligible only if they can no longer have children.
This landmark trial represents a significant advancement in the treatment approach for ATTR-CM (search), potentially offering new hope to patients suffering from this debilitating condition. If successful, it would mark the first application of DNA-altering treatment in adult cardiology, potentially transforming the management of this rare cardiac disease.