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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 6 Mo
Max Age: 12 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women


Lysosomal Diseases

Recruitment Keyword(s)



Lysosomal Diseases;

Investigational Drug(s)


Investigational Device(s)



Biological/Vaccine: AAV9-GLB1
Procedure/Surgery: Abdominal ultrasound
Drug: Rituximab
Drug: Sirolimus
Drug: Methylprednisolone
Drug: Prednisone
Diagnostic Test: Audiology assessment with ABR
Diagnostic Test: Bone density scan (DEXA)
Diagnostic Test: Electrocardiogram (EKG)
Diagnostic Test: Echocardiogram
Other: Electroencephalogram (EEG) awake and extended overnight
Diagnostic Test: Laboratory tests
Procedure/Surgery: Lumbar puncture
Procedure/Surgery: Brain MRI/MRS/fMRI
Behavioral: Neurocognitive testing
Other: Neurology exam
Behavioral: PICC or other Central line placement
Procedure/Surgery: Skeletal survey
Procedure/Surgery: Skin biopsy
Procedure/Surgery: Speech and modified barium swallow study
Procedure/Surgery: Ophthalmology exam

Supporting Site

National Human Genome Research InstituteSio Gene Therapies


GM1 gangliosidosis is a disorder that destroys nerve cells. It is fatal. There is no treatment. People with GM1 are deficient in a certain enzyme. A gene therapy may help the body make this enzyme. This could improve GM1 symptoms.


To test if a gene therapy helps Type I and Type II GM1 gangliosidosis symptoms.


Type I subjects will be male and female >= 6 months <= 12 months of age at the time of full ICF signing.

Type II subjects will be male and female > 12 months old and < 12 years old at the time of full ICF signing.


Participants will be screened with their medical history and a phone survey.

Participants will stay at NIH for 8-10 weeks.

Participants will have baseline tests:

Blood, urine, and heart tests

Hearing tests

Ultrasound of abdomen

EEG: Sticky patches on the participant s head will measure brain function.

Lumbar puncture: A needle will be stuck into the participant s spine to remove fluid.

MRI scans, bone x-rays, and bone scans: Participants will lie in a machine that takes pictures of the body

IQ tests

Neurology exams

Central line placement

Skin biopsy: A small piece of the participant s skin will be removed.

Speech tests

Participants will have an x-ray while swallowing food.

Participants will take drugs by mouth and IV. This will get their immune system ready for therapy.

Participants will get the gene therapy by IV. They may stay at NIH for a week to watch for side effects.

Participants will have visits 3 and 6 months after treatment. Then visits will be every 6 months for 2 years. Then they will have a visit at 3 years. Visits will take 4-5 days.

Participants will return to NIH once a year for 2 years for tests in an extension study.

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Type I subjects

- 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

Type II subjects

- 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


- 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, 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:

-- Falling 20 percentiles (20/100) in body weight in the 3 months preceding Screening/Baseline

- Underlying defect in immune function

- History of multiple and severe life-threatening infections

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Cynthia J. Tifft, M.D.
National Human Genome Research Institute (NHGRI)
NIHBC 10 - CRC BG RM 3-2551
(301) 451-8485

Jean M. Johnston
National Human Genome Research Institute (NHGRI)
National Institutes of Health
Building 10
Room 3-2551
10 Center Drive
Bethesda, Maryland 20892
(240) 515-1448

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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