A Natural History Study of the Gangliosidoses

Brief Title

A Natural History Study of the Gangliosidoses

Official Title

A Natural History Study of the Gangliosidoses

Brief Summary

      Hypothesis: To characterize and describe disease progression and heterogeneity of the
      gangliosidosis diseases.

      This research study seeks to develop a quantitative method to delineate disease progression
      for the gangliosidosis diseases (Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis)
      in order to better understand the natural history and heterogeneity of these diseases. Such a
      quantitative method will also be essential for evaluating any treatments that may become
      available in the future, such as gene therapy. The data from this study will be necessary to
      provide end-points for future therapies, guide medical decisions about treatment, provide
      objective measurement of treatment outcomes, and accurately inform parents regarding
      potential outcomes.

Detailed Description

      The infantile form of GM2 and GM1 gangliosidosis diseases ("classic" infantile) is the most
      common. Infants with Tay-Sachs disease, Sandhoff disease or GM1 gangliosidosis appear normal
      at birth, but at approximately 6-10 months of age begin to manifest progressive weakness and
      loss of muscle strength, such as loss of the ability to sit up or turn over. They may
      evidence deafness, and display decreased attentiveness. This is followed by rapid
      deterioration of motor skills and slowed mental development (neurodegeneration), often with
      seizures. Retinal involvement leads to visual impairment and eventual blindness. Death
      typically occurs by the age of five. Currently there is no treatment for Tay-Sachs disease,
      Sandhoff disease or GM1 gangliosidosis.

      Late Onset Tay-Sachs disease ("LOTS") occurs in patients beginning in their twenties or
      thirties, and is characterized by poor motor coordination and psychotic behaviors. Patients
      with LOTS also have decreased life expectancy, although to a lesser degree than those with
      infantile or juvenile Tay-Sachs or Sandhoff diseases. Currently there is no treatment for

      This study is comprised of two different 'arms.' The first arm, entitled Aim 1, will focus on
      the developmental course of infantile and juvenile Tay-Sachs disease, Sandhoff disease, and
      GM1 gangliosidosis. Longitudinal data from individuals with these diseases will be collected
      in order to delineate the natural history of these diseases. This data will help to objectify
      disease progression, and can be used to create a disease stage and severity index.

      The second arm, entitled Aim 2, will focus on LOTS and will seek to understand the
      progression of central nervous system disease, with special focus upon cerebellar and frontal
      systems. This will be accomplished by using quantitative methods including neuroimaging and
      neuropsychological measures that explore motor and executive functions, visual-spatial and
      emotional-behavioral dysfunction.

Study Type


Primary Outcome

Change in Child Developmental Status as Assessed by Neuropsychological Tests

Secondary Outcome

 Ascertainment of Enzyme Activity Levels


Tay-Sachs Disease

Study Arms / Comparison Groups

 Gangliosidosis Diseases Study Population
Description:  This study observes one cohort: 42 infantile or juvenile Tay-Sachs disease, Sandhoff disease, or GM1 gangliosidosis affected subjects; and 10 late-onset gangliosidosis disease affected subjects.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

December 2010

Completion Date

March 1, 2027

Primary Completion Date

March 1, 2027

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must have a documented gangliosidosis disease.

          2. Subjects must be able to complete appropriate neuropsychological and neurobehavioral

          3. Late-onset gangliosidosis subjects must be able to tolerate a head MRI.

        Exclusion Criteria:

        1. There are no exclusion criteria, beyond a desire not to participate.




N/A - N/A

Accepts Healthy Volunteers



Jeanine R. Jarnes, PharmD, 612-626-5131, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

University of Minnesota


 Rare Diseases Clinical Research Network

Study Sponsor

Jeanine R. Jarnes, PharmD, Principal Investigator, University of Minnesota - Fairview

Verification Date

March 2023