Miglustat as a treatment for adults with Tangier Disease neuropathy: the MUSTANG N-of-1 trial with 21 months clinical observation.
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 was designed 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 benefit 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.
Date
2025-11-10
Type
Article
Subject
Metabolic Diseases, Rare Diseases, Neurologic Manifestations
Collections
Citation
Cook A, Stuart B, Ochoa-Ferraro A, Condon N, Lawrence M, Webley F, Wallom KL, Forbes C, Veeranna V, Wanninayake S, Oliver T, Davies N, Dawson C, Platt F, Hiwot T. Miglustat as a Treatment for Adults with Tangier Disease Neuropathy: The MUSTANG N-of-1 Trial with 21 months Clinical Observation. Neurol Ther. 2025 Nov 10. doi: 10.1007/s40120-025-00843-6.
Journal / Source Title
Neurology and Therapy
DOI
10.1007/s40120-025-00843-6
PMID
41212481
Publisher
Springer
Publisher’s URL
https://pubmed.ncbi.nlm.nih.gov/41212481/#full-view-affiliation-4