Condition category
Nutritional, Metabolic, Endocrine
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Background and study aims
Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare genetic disorder. There are four types (A to D). Sanfilippo syndrome subtype B, or mucopolysaccharidosis type IIIB (MPSIIIB), is caused by a genetic defect of the enzyme α-N-acetylglucosaminidase (NAGLU). This enzyme is involved in breaking down long chains of sugar molecules. In its absence, these molecules build up. This causes brain damage starting most often during the first 5 years of life. Affected children require specific care and death occurs at the average age of 15, although some patients are still alive after the age of 20. MPSIIIB could be treated by delivering the correct gene for the missing enzyme using a virus (gene therapy). The aim of this study is to test this gene therapy approach in patients with MPSIIIB.

Who can participate?
Patients age 18 months to 5 years with MPSIIIB

What does the study involve?
Participants receive gene therapy combined with immunosuppressant drugs (to suppress the strength of the body's immune system). The virus is injected into the brain at 6 injection sites in a single session. Clinical and x-ray examinations are carried out and blood and cerebrospinal fluid samples are taken before and after treatment, with daily follow-up during 1 week after the injections, then 14 and 21 days, 1, 3, 6 and 12 months after treatment.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Hôpital Bicêtre (France)

When is the study starting and how long is it expected to run for?
September 2013 to November 2015

Who is funding the study?
1. French Patient Association (France)
2. Private donations (France)

Who is the main contact?
Prof. Marc Tardieu

Trial website

Contact information



Primary contact

Prof Marc Tardieu


Contact details

Service de Neurologie Pédiatrique
Hôpital Bicêtre
Assistance Publique - Hôpitaux de Paris
rue du Général Leclerc
Le Bicêtre-Bicêtre

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A phase I/II, open-label, study of intracerebral administration of adeno-associated viral vectors carrying human NaGlu cDNA for the treatment of Sanfilippo type B syndrome



Study hypothesis

There is currently no available treatment for Sanfilippo syndrome. The rationale for therapeutic approaches in mucopolysaccharidoses (MPS) is based on the observation that delivery of the missing enzyme reverses phenotypic abnormalities in genetically deficient cells. Although enzyme replacement therapy (ERT) is being explored, there is still not currently available for MPSIIIB.

On the other hand, MPS have long been recognized as prime candidate diseases for gene therapy as it was shown that the missing enzyme may be produced and distributed to the organism by a group of genetically modified cells.

Indeed, numerous studies in animal models of MPS have described the effects of genetic modification of tissues including bone marrow, skin, muscle, liver and brain, resulting in the production of a therapeutically active enzyme.

However, when vectors are administered in the periphery, the produced enzymes do not cross the blood-brain barrier. Only very high doses of enzyme in the circulation may result in detectable transport into the brain.

In MPSIII, a direct administration into the brain would be required, since most lesions take place in this organ.

Ethics approval

CCP Il-de-France II, 17/04/2013, ref: 2013-03-17

Study design

Phase I/II single-arm open-label study

Primary study design


Secondary study design

Non randomised study

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Mucopolysaccharidose - neurodegenerative disease


Patients will receive gene therapy combined with immunosuppressant regimen. The vector is a serotype 2 AAV genome encoding the human α-N-acetylglucosaminidase cDNA packaged in a serotype 5 capsid called AAV-NAGLU. Vector suspensions will be simultaneously injected into the brain parenchyma at 6 injections sites in a single neurosurgical session. Combined immunosuppression (Tacrolimus, Cell-Cept) is justified by previous studies in children receiving recombinant enzyme infusions and investigations of AAV-mediated gene therapy in Sanfilippo and Hurler dogs.

Clinical and radiological examination, collection of biological products including blood, peripheral blood mononucleated cells and cerebrospinal fluid (CSF) > 6 weeks prior to treatment, at inclusion, baseline, 14 days prior to treatment, observation and -2 and -1 days, daily follow-up during 1 week post-injection, then 14 and 21 days, 1, 3, 6 and 12 months post-treatment.

The total duration of follow up is 1 year.

Added 02/08/2013:
Vectors will be delivered through 8 small burr holes. Two in the posterior fossa to target the white matter of the cerebellar hemisphers and six supratentorially, to target the white matter adjacent to the putamen. Two deposits will be done on each track, one deep and one superficial, in a single neurosurgical session.

Intervention type



Phase I/II

Drug names

Intra-cerebral gene therapy

Primary outcome measure

Clinical, radiological, biological tolerance associated to the proposed treatment

Secondary outcome measures

Collection of data to define exploratory tests that will become evaluation criteria for further clinical phase III efficacy studies (brain MRI; neurological and biological markers)

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Age: 18 months to the end of the 5th year
2. Onset of clinical manifestations related to MPSIIIB during the first 5 years of life
3. NaGlu activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls
4. Patient affiliated to a social security regimen
5. Family understanding the procedure and the informed consent
6. Vital laboratory parameters within normal range

Sanfilippo disease is a rare disease and so the countries of recruitment will depend on the availabilities of the patient at the time of recruitment. There will be one study centre in France.

Participant type


Age group




Target number of participants

4 children from Europe

Total final enrolment


Participant exclusion criteria

1. Presence of brain atrophy on pre-inclusion MRI judged on a cortico-dural distance of more than 1 cm
2. Any condition that would contraindicate permanently anaesthesia
3. Any other permanent medical condition not related to MPSIIIB
4. No independent walking (Ability to walk without help)
5. Any vaccination 1 month before vector injection
6. Receipt of aspirin within one month
7. Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Hôpital Bicêtre
Le Bicêtre-Bicêtre

Sponsor information


Institut Pasteur (France)

Sponsor details

25-28 Rue du Dr Roux

Sponsor type




Funder type


Funder name

French Patient Association (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Private donations (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2017 results in (added 18/12/2020)

Publication citations

Additional files

Editorial Notes

18/12/2020: The following changes were made to the trial record: 1. Publication reference added. 2. The total final enrolment was added. 11/05/2017: Plain English summary added. 06/08/2013: The overall trial start date was changed from 01/06/2012 to 01/09/2013 and the overall trial end date was changed from 01/12/2015 to 01/11/2015. 02/08/2013: The target number of participants was changed from 8 to 4.