Cook, Andrew, Stuart, Beth, Ohoa-Ferraro, Antonio, Condon, Nicola, Lawrence, Megan, Webley, Frances H, Wallom, Kerri-Lee, Forbes, Claire P, Veeranna, Vishy, Wanninayake, Subadra, Oliver, Tom, Davies, Nicholas, Dawson, Charlotte, Platt, Frances M. and Geberhiwot, Tarekegn (2025) Miglustat as a treatment for adults with tangier disease neuropathy: The MUSTANG N‑of‑1 Trial with 21 months clinical observation. Neurology and Therapy. (doi:10.1007/s40120-025-00843-6).
Abstract
Importance: Tangier disease (TD) is an ultra- rare disease, characterised by progressive peripheral neuropathy with no established treatment.
Objectives: To determine whether miglustat improved the clinical status of a single patient with TD, and to investigate the possible mechanisms of miglustat in this patient.
Design, Setting, and Participants: An n-of-1 ABAB study, alternating on and off treatment for 6-month periods, total study duration of 2 years with an additional compassionate-access period of 21 months.
Exposure: Miglustat, an orphan drug licenced to treat Gaucher disease and Niemann–Pick disease, was repurposed.
Main Outcomes and Measures: The study wasdesigned with two co-primary endpoints: (a) time taken to complete the nine-hole peg test
(fine motor control and finger dexterity), and (b) hand strength: grip and three-point pinch strength tests. Secondary endpoints were quality-of-life measures and biomarkers.
Results: A 21-year-old (at baseline) left-handed male patient with TD, diagnosed at the age of 6 months, and disabling neuropathy was included in the study. Over 2 years, there was a small signal in our clinical measures that the drug may be beneficial. Compared with the 2 years prior to treatment, the patient had no relapse of neuropathy during his study period and further extension. During the 21-month treatment extension, he showed considerable improvement on primary endpoints. Biomarkers changed as expected based on the mechanism of action of miglustat. Nerve conduction studies showed a mild benefit. Importantly, the patient’s reported experience suggested a meaningful ben efit from miglustat.
Conclusions and Relevance: Miglustat may be used to treat neurological complications of TD. This study showed that an n-of-1 study to inform a policy decision is practical and may offer hope to patients with rare diseases.
Trial Registration: ClinicalTrials.gov Identifier: ISRCTN17945917. Registration date: 07/06/2021; ‘retrospectively registered’.
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