SINGAPORE – A new drug based on gene-editing technology could soon provide respite to patients suffering from a rare and potentially fatal genetic heart disease.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare disease of the heart muscle that involves deformed transthyretin (TTR) proteins building up in the heart, nerves and other organs.

As a result of the protein build-up, the walls of the heart become thickened and stiff. The heart cannot then relax properly and get filled with blood, and it cannot pump it efficiently to the rest of the body.

The symptoms of ATTR-CM can be vague and may include numbness in the hands and feet, lethargy and dizziness; but left undiagnosed and not treated promptly, it could lead to heart failure and death. 

The disease affects about 150 people in Singapore, but Assistant Professor Lin Weiqin – clinical director for the heart failure and cardiomyopathy programme at the National University Heart Centre, Singapore (NUHCS) – believes the number could be much higher.

This is because those affected often dismiss the symptoms – including swelling in the legs, numbness in the hands and unsteady walking – as normal consequences of ageing, Prof Lin said, noting that such symptoms can also be attributed to other conditions.

“Not many patients know about this condition, and not many doctors can diagnose this condition accurately as well,” he said, noting that NUHCS first set up a registry for ATTR-CM patients in 2019.

Nexiguran Ziclumeran, a new drug that is also known as nex-z or NTLA-2001, seeks out and removes a portion of the TTR gene, slowing down the production of the disease-causing protein.

It is based on Crispr-Cas9 technology, the Nobel Prize-winning gene-editing tool which has been used to alter DNA sequences.

US biotechnology firm Intellia Therapeutics, which developed nex-z, is now conducting a worldwide trial involving 765 patients with ATTR-CM and a history of heart failure to evaluate its efficacy.

Recruitment for the double-blind trial – where neither the participants nor the researchers know who received the actual treatment and who received a placebo – in Singapore began in 2024.

Eight patients have already been recruited from NUHCS and the National Heart Centre Singapore, and Prof Lin, who is leading the study here, said they hope to recruit a total of 14 patients by end-2025.

Prof Lin noted gene editing therapy has already been approved in other countries for...