NUHCS leads the Singapore arm of the world's first gene editing trial in adult cardiology, targeting the root cause of ATTR-CM
PULSE Issue 45 | July 2025
In a bold stride toward tackling a rare but life-threatening heart condition, Asst Prof Lin Weiqin, Clinical Director of Heart Failure and Cardiomyopathy Programme, Department of Cardiology, NUHCS, is leading the Singapore arm of the international MAGNITUDE trial – a global study exploring the potential of gene editing to treat Transthyretin Amyloid Cardiomyopathy (ATTR-CM). If successful, this initiative will be the first DNA altering treatment used in the field of adult
cardiology.
Understanding ATTR-CM
ATTR-CM is a progressive condition caused by accumulation of misfolded transthyretin proteins in the heart and other organs. Due to the accumulation of protein, the heart’s walls become thick and rigid, preventing the heart from efficiently pumping blood to the rest of the body. These proteins disrupt normal function and lead to symptoms such as numbness, fatigue and dizziness. If not diagnosed and treated promptly, ATTRCM can lead to heart failure. The condition may arise due to a genetic mutation or as part of the natural ageing process.
Unfortunately, there is currently no cure for this debilitating illness.
The disease affects an estimated 150 people in Singapore, but numbers could be more as symptoms – including stiffness of limbs and fatigue – are often dismissed as part of the ageing process or attributed to other medical conditions. For patients like Mr Chua Ah Hai, who was diagnosed with ATTR-CM while receiving treatment after a car accident ten years ago, this disease has significantly impacted his quality of life. Despite ongoing medication, his symptoms continue to worsen. The once active 62-year-old can now no longer walk due to the stiffening of his hands and legs by the disease, leading to repeated hospitalisations and increasing disability. However, through this new clinical trial, a glimmer of hope has emerged – not just for him, but also for others facing the same struggle.
A Global First in Adult Cardiology
The MAGNITUDE study – led locally by Asst Prof Lin – investigates a single-dose gene editing therapy called Nexiguran Ziclumeran (NEX-z), also known as NTLA-2001, designed to alter the patient’s DNA and reduce production of the harmful transthyretin protein at its source. Although full results may take two to three years, early findings have shown promising results with consistent, rapid, and sustained reductions in abnormal protein levels, with minimal side effects – pointing toward a safer, more effective treatment option for those with ATTR-CM.
Pioneering with Purpose
Through this initiative, NUHCS is not only reaffirming its leadership in cardiovascular care but also bringing new, potentially life-changing treatments closer to home for patients within Asia. By advancing science with compassion, discoveries can be translated into real, tangible hope for patients, caregivers, and families affected by rare diseases like ATTR-CM.
If this trial is successful, gene editing therapy will be the first DNA altering treatment used in adult cardiology and offers new hope to patients living with ATTR-CM.
- Asst Prof Lin Weiqin, Clinical Director of Heart Failure and Cardiomyopathy Programme, Department of Cardiology, NUHCS
Read how science is reshaping the fight against ATTR-CM in this The Straits Times article.
