The FDA told uniQure that its AMT‑130 gene‑silencing therapy for Huntington’s disease will require a prospective, randomized, double‑blind, sham‑surgery‑controlled study to support marketing approval, overruling reliance on Phase I/II external‑control comparisons. AMT‑130 previously showed strong signals of slowing progression in early trials, prompting praise from patient advocates and clinicians. Regulatory counsel and clinicians warned the agency’s demand raises ethical and feasibility questions, as sham brain surgery would delay treatment for control participants potentially for years and could render some patients ineligible for later intervention. The decision underscores heightened evidentiary standards for one‑time CNS gene therapies and sets a precedent affecting other neurodegenerative programs.