Breakthrough in Gene Therapy Stabilizes Neuropathy in Rare Nerve Disease

Researchers from University College London's National Amyloidosis Center have reported promising results from a novel gene editing therapy for hereditary transthyretin amyloidosis with polyneuropathy, a serious and often fatal nerve disorder. The therapy, named nexiguran ziclumeran, involves a single infusion that significantly lowers serum transthyretin (TTR) protein levels. TTR is responsible for amyloid deposits in tissues, which cause nerve and organ damage.

In a multinational Phase I trial involving 36 patients across France, New Zealand, Sweden, and the UK, the treatment resulted in rapid, profound, and sustained reductions in TTR levels — a decrease of approximately 90% at 28 days and over 92% at 24 months. Notably, most patients' neuropathy scores remained stable or improved over the 24-month period, indicating a potential halt or slowdown in disease progression.

Hereditary transthyretin amyloidosis is characterized by the abnormal accumulation of misfolded TTR protein in peripheral nerves, leading to progressive nerve damage. The disease's median survival ranges from six to twelve years after onset, with current available treatments requiring ongoing administration and only partial efficacy.

This study, published in The New England Journal of Medicine, highlights the possible of gene editing to produce durable disease modification. The therapy was generally well-tolerated, with side effects mostly related to infusion reactions, headaches, diarrhea, and some changes in thyroid hormone levels. Serious adverse events included one death due to cardiac amyloidosis.

The findings suggest that a one-time gene editing approach like nexiguran ziclumeran could revolutionize the treatment landscape for this devastating disease, leading to more effective and less burdensome management options. Further research is ongoing to confirm long-term safety and efficacy.

Source: https://medicalxpress.com/news/2025-10-stabilization-neuropathy-scores-gene-therapy.html