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Gene Therapy for GM1 Gangliosidosis (Type I and Type II)

This study is testing a gene therapy called AAV9-GLB1 for children with Type I and Type II GM1 gangliosidosis, a severe disease that damages nerve cells. Currently, there is no cure for GM1 gangliosidosis. The goal of this study is to see if AAV9-GLB1 can help the body make a missing enzyme, beta-galactosidase, which could improve symptoms. Participants will also receive other medications like Rituximab, Sirolimus, and Methylprednisolone to help manage their immune system's response to the gene therapy. The main focus is to understand the safety of this treatment over three years. Children between 6 months and 12 years old with a confirmed diagnosis of GM1 gangliosidosis may be eligible.

Study design
This is a Phase 1/2 interventional study, meaning it's an early-stage trial to assess safety and initial effectiveness. It is a non-randomized study with a planned enrollment of 54 participants.
What's involved
Participants will undergo screening, including medical history and a phone survey. They will stay at the NIH for 8-10 weeks and have abdominal ultrasounds as part of screening and safety follow-up.
Compensation
Not stated in the trial record.
Follow-up
Safety will be measured at several time points over three years after treatment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT03952637

A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis

Recruiting
PHASE1Ages 6–12InterventionalTreatment
National Human Genome Research Institute (NHGRI)
~54 participants
Updated 2026-09-11 on ClinicalTrials.gov
What's tested:AAV9-GLB1Abdominal ultrasoundRituximabSirolimusMethylprednisolonePrednisone

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Safety
Measured over Several time points over 3 years

Conditions

Lysosomal Diseases
Gangliosidosis
GM1

Explore related trials

GM1 GangliosidosisAAV9Beta-Galactosidase

NCT03952637

Where you'd take part

This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • National Institutes of Health Clinical Center

    Bethesda, Marylandstudy coordinator listed

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Cynthia J Tifft, M.D. · PRINCIPAL_INVESTIGATOR · National Human Genome Research Institute (NHGRI)

Who to contact

Jean M Johnston
[email protected]
(240) 515-1448
Email the study team

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Eligibility criteria

Inclusion

Male or female subjects \>= 6 months old and \<= 12 months old at time of full ICF signing
Biallelic mutations in GLB1
Documented deficiency of Beta-galactosidase enzyme by clinical laboratory testing
Phenotype consistent with a diagnosis of Type I GM1 gangliosidosis
Symptomatic subjects: as determined by the opinion of the Principal Investigator and based on the criteria set forth by Brunetti-Pierri et al:
Age of symptom onset \<= 6 months of age
Rapidly progressive with developmental delay and hypotonia
Pre- symptomatic subjects: must have mutations confirmed to be associated with the Type I subtype
AAV9 antibody titers \<=1:50
Agree to reside within 50 miles of the study site for at least 1 month following treatment
Vineland-3 Adaptive Behavior composite standard score greater than or equal to 40
Male or female subjects \> 6 months old and \< 12 years old at time of full ICF signing
Biallelic mutations in GLB1
Documented deficiency of beta-galactosidase enzyme by clinical laboratory testing
Phenotype consistent with a diagnosis of Type II GM1 gangliosidosis, with symptom onset after the first year of life
AAV9 antibody titers \<=1:50
Agree to reside within 50 miles of the study site for at least 1 month following treatment

Exclusion

AAV9 antibody titers \>1:50
Contraindications to concomitant medications
Serious illness that would not allow travel to the study site
Unwilling to undergo study interventions as outlined in the Schedule of Events
Subjects receiving other unapproved, off-label or experimental therapies for GM1 gangliosidosis (i.e. miglustat, Tanganil) within the last 60 days
Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
Pregnant or lactating subjects
Immunizations of any kind in the month prior to screening
Evidence of cardiomyopathy on history, exam, or additional testing (echocardiogram or electrocardiogram) or other cardiac disease that in the opinion of the investigator would deem the subject unsafe to participate in the trial
Indwelling ferromagnetic devices that would preclude MRI/fMRI/MRS imaging
Ongoing medical condition that is deemed by the Principal Investigator to interfere with the conduct or assessments of the study
History of infection with human immunodeficiency virus (HIV), hepatitis A, B, or C, or tuberculosis.
History of or current chemotherapy, radiotherapy or other immunosuppressive therapy within the past 30 days. Corticosteroid treatment may be permitted at the discretion of the PI
Abnormal laboratory values considered clinically significant per the investigator
Failure to thrive, defined as:
Underlying defect in immune function
History of multiple and severe life-threatening infections

What this trial measures

  • SafetySeveral time points over 3 years

    Assess the safety of the AAV9/GLB1 vector (AAV9-GLB1) following intravenous delivery.