Synergistic Enteral Regimen for Treatment of the Gangliosidoses
Condition: GM1 Gangliosidoses; GM2 Gangliosidoses; Tay-Sachs Disease; Sandhoff Disease
MeSH terms: Gangliosidoses; Tay-Sachs Disease; Gangliosidosis, GM1; Gangliosidoses, GM2; Sandhoff Disease
Intervention: miglustat; Ketogenic Diet
Intervention description: The Syner-G therapy regimen includes treating with orally-administered miglustat for the duration of the 60-month study.; The Syner-G therapy regimen includes switching the research subject to a full-time ketogenic diet for the 60-month duration of this study.
Intervention MeSH terms: Miglustat
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Maximum age: 204 Months
Healthy volunteers: No
Keywords: infantile Tay-Sachs disease; juvenile Tay-Sachs disease; infantile GM1 gangliosidosis; juvenile GM1 gangliosidosis; infantile GM2 gangliosidosis; juvenile GM2 gangliosidosis; Sandhoff disease; gangliosidoses; miglustat; ketogenic diet; SYNER-G regimen; Syner-G; Zavesca; Tay-Sachs disease; Tay Sachs disease

Summary:

      The investigators hypothesize that a combination therapy using miglustat and the ketogenic
      diet for infantile and juvenile patients with gangliosidoses will create a synergy that 1)
      improves overall survival for patients with infantile or juvenile gangliosidoses, and 2)
      improves neurodevelopmental clinical outcomes of therapy, compared to data reported in
      previous natural history studies. The ketogenic diet is indicated for management of seizures
      in patients with seizure disorders. In this study, the ketogenic diet will be used to
      minimize or prevent gastrointestinal side-effects of miglustat. A Sandhoff disease mouse
      study has shown that the ketogenic diet may also improve central nervous system response to
      miglustat therapy (see Denny in "Citations" list below). Patients with infantile and juvenile
      gangliosidoses commonly suffer from seizure disorders, and use of the ketogenic diet in these
      patients may therefore also improve seizure management.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must have a documented infantile or juvenile gangliosidosis disease.

          2. Age: 17 years or less at time of enrollment

          3. Subjects and their caregivers must be willing to work with a ketogenic diet team for
             management of the subject's ketogenic diet.

        Exclusion Criteria:

          1. A desire to not participate

          2. Patients who are older than 17 years will not be enrolled in this study.

          3. Children with severe renal impairment will not be enrolled in this study.

          4. Post-pubertal females who are pregnant, or who are unwilling to use highly-effective
             methods to prevent pregnancy, will be excluded from this study.

          5. Breast-feeding females will be excluded from this study.

          6. Subjects who have an allergy to miglustat or any of the components within the drug
             product will be excluded from this study.