Substrate reduction therapy in juvenile GM2 gangliosidosis

Gustavo H.B. Maegawa, Brenda L. Banwell, Susan Blaser, Geoffrey Sorge, Maggie Toplak, Cameron Ackerley, Cynthia Hawkins, Jason Hayes, Joe T.R. Clarke

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Substrate reduction therapy (SRT) is considered to be a potential therapeutic option for juvenile GM2 gangliosidosis (jGM2g). We evaluated the efficacy of SRT in jGM2g, assessing neurological, neuropsychological and brain magnetic resonance imaging (MRI) outcomes over a 24-month period of treatment. In an open-label and single-center study, five jGM2g patients (mean age 14.6 ± 4.5 years) received oral miglustat at doses of 100-200 mg t.i.d. adjusted to body surface area. Patients underwent general and neurological examinations, neuropsychological, electrophysiological, and brain MRI studies. All patients showed neurological deterioration over the period of the study, with particularly notable worsening of gait, speech and coordination. One patient experienced acute psychosis, and another showed worsening of pre-existing epilepsy. Some neuropsychological tests showed no evidence of deterioration in the three patients with high enough cognitive functioning for reliable assessment. Profound cognitive impairment in two children precluded neuropsychological evaluation. In four patients, evaluation of brain MRI showed no changes in white matter signal abnormalities and cerebellar atrophy noted at baseline, while one patient showed progression of cerebellar and supratentorial brain atrophy. Transmission electron microscopy analysis of peripheral mononuclear cells showed reduction of intracytoplasmatic inclusions with treatment. SRT with miglustat of patients with jGM2g failed to ameliorate progressive neurological deterioration, but apparently no worsening of some areas of cognitive function tested and brain MRI lesions was noted over 24 months of treatment. The results must be interpreted with care owing to the small sample of patients and the lack of a control-arm.

Original languageEnglish (US)
Pages (from-to)215-224
Number of pages10
JournalMolecular genetics and metabolism
Issue number1-2
StatePublished - Oct 2009


  • Juvenile GM2 gangliosidosis
  • Miglustat
  • Sandhoff disease
  • Substrate reduction therapy
  • Tay-Sachs disease

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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