Synergistic Enteral Regimen for Treatment of the Gangliosidoses

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).

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.