Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G)

• The duration of survival of each research subject, measured in months and years [ Time Frame: From date of enrollment until 60 months thereafter, or the date of subject's death from any cause, whichever comes first, assessed up to 60 months ] [ Designated as safety issue: No ]
  The survival duration of patients with infantile and juvenile forms of gangliosidoses will be assessed, in order to judge the clinical impact of the Syner-G therapy regimen. This will be accomplished by recording the subject's age on the date of enrollment in this study, and the subject's age at the conclusion of this study, or on the date of their death, whichever comes first. The duration of each subject's survival, expressed in months and years, will be compared to available natural history data in order to arrive at an expert assessment of the impact of the Syner-G therapy upon patient longevity.
  
  

• Rate of Change in Neurocognitive Functioning [ Time Frame: Upon Enrollment, and thereafter at 12, 24, 36, 48 and 60 months post-enrollment ] [ Designated as safety issue: No ]
  The Bayley Scales of Infant and Toddler Development and the Vineland Adaptive Behavior Scales will be administered upon enrollment and annually thereafter for five years. Changes in these neurodevelopmental assessments will be evaluated over the duration of follow-up. Ability of the child to have these assessments yearly may be subject to patient's insurance coverage for such assessments.
  
  

The infantile and juvenile forms of GM1 and GM2 gangliosidoses are neurodegenerative conditions that are lethal during childhood. There are no known effective therapies available for treatment of infantile and juvenile gangliosidoses. Studies of monotherapy with miglustat for treatment of these conditions have demonstrated safety, but have not demonstrated notable clinical improvement. To date, combination therapy for the infantile and juvenile gangliosidoses has not been explored. This study will evaluate a multi-targeted combination therapy for treatment of the gangliosidoses, using FDA approved therapies that have demonstrated safety in children. It is the aim of this study to learn if combination therapy using the "Syner-G" regimen (that is, synergistic enteral regimen for treatment of the gangliosidoses) will show improvement in overall survival and clinical benefits in neurodevelopmental abilities in children with gangliosidosis diseases.

This study is planned as a 5-year longitudinal treatment study. Subjects will be started on the treatment regimen when they are enrolled in the study. Data will be collected during yearly evaluations and at completion of study. Investigators may choose to stop therapy at any time, as clinically indicated for individual patients.

The Ketogenic Diet is a special diet that contains higher amounts of fat and lower amounts of carbohydrate compared to an average diet. The purpose of this is to help reduce food-miglustat interactions. The ketogenic diet may also help in management of seizures in these patients. (The ketogenic diet has been used as an anti-seizure treatment in a variety of medical conditions for many decades.) A study in Sandhoff disease mice has shown that the ketogenic diet may also help miglustat be more effective in the central nervous system (see Denny in "Citations" list below).

Miglustat will be used to reduce the amount of ganglioside accumulation in the child's cells. Miglustat is not FDA approved for treatment of the gangliosidoses. It is FDA approved for a different inherited metabolic disease called Gaucher disease type I.

This study has been issued Investigational New Drug (IND) # 127636 by the U.S. Food and Drug Administration (FDA).