Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment.
OBJECTIVE
To evaluate the safety and efficacy of miglustat in patients with GM2 gangliosidosis.


METHODS
A randomized, multicenter, open-label, 12-month study involving patients aged 18 years or older, randomized 2:1 to miglustat (200 mg TID) or "no miglustat treatment." This study was followed by 24 months of extended treatment during which all patients received miglustat. Primary efficacy endpoints were change in eight measures of isometric muscle strength in the limbs and isometric grip strength, evaluated at baseline, and months 12 and 36. Secondary efficacy endpoints included gait, balance, disability, and other neurological assessments. Safety evaluations included adverse event reporting.


RESULTS
Thirty patients (67% male, age range 18-56 years) with late-onset Tay-Sachs disease were enrolled; 20 were randomized to miglustat and 10 to "no miglustat treatment." Muscle and grip strength generally decreased over the study period. No differences were observed between the two groups in any efficacy measure, either during the 12-month randomized phase or the full 36 months. The most common treatment-related adverse events were decrease in weight and diarrhea.


CONCLUSIONS
Miglustat treatment was not shown to lead to measurable benefits in this cohort of patients with late-onset Tay-Sachs disease. The observed safety profile was consistent with that of the approved dose (100 mg TID) in type 1 Gaucher disease.
Shapiro
Barbara E
BE
Department of Neurology, University Hospitals Case Medical Center, Cleveland, Ohio 44106-5098, USA. bes002@aol.com
Pastores
Gregory M
GM
Gianutsos
John
J
Luzy
Cécile
C
Kolodny
Edwin H
EH
D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D003967:Diarrhea / Q000139:chemically induced; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D013661:Tay-Sachs Disease / Q000188:drug therapy* / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat