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CompletedNCT01801709TG-MLDUpdated Mar 2, 2026

Intracerebral Gene Therapy for Children With Early Onset Forms of Metachromatic Leukodystrophy

A Phase 1/2 interventional study of intracerebral administration of AAVrh.10cuARSA in Metachromatic Leukodystrophy, sponsored by Institut National de la Santé Et de la Recherche Médicale, France. Completed at 1 site in France. Open to participants aged 6 Months to 5 Years. Per ClinicalTrials.gov, last updated 2026-03-02.

Sponsored by Institut National de la Santé Et de la Recherche Médicale, France · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
5
Allocation
Not applicable
Ages
6 Months to 5 Years
Sex
All
01

Study summary

The objective of this open-label, single arm, monocentric, phase I/II clinical study is to assess safety and efficacy of ARSA gene transfer in the brain of children affected with early onset forms of Metachromatic Leukodystrophy (MLD). For this purpose, an adeno-associated virus serotype rh.10 (AAVrh.10) vector will be used to transfer the ARSA cDNA coding for Arylsulfatase A (ARSA) enzyme into the brain of children. Five patients with early onset form of MLD, age ranging from 6 months to 4 years, will be included in this protocol and will be followed during 24 months.

Patients will be selected at presymptomatic or early stage of their disease, following clinical, neuropsychological and brain imaging criteria.

Twelve simultaneous injections of the investigational medicinal product will be performed in the white matter of both brain hemispheres, through 6 image-guided tracks, with 2 deposits per track.

A low dose (1x10EXP12 vg total) will be administered to the first 2 patients, while the last 3 will receive a higher dose (4x10EXP12 vg total).

Safety and efficiency will be evaluated based on clinical, neuropsychological, radiological, electrophysiological and biological parameters.

02

Conditions studied

  • Metachromatic Leukodystrophy

Keywords

  • Brain Gene Therapy
  • Adeno Associated vector
  • Lysosomal sotage diseases
  • Leukodystrophies
03

In context

Leukodystrophy, Metachromatic

42 studies on the registry are indexed under Leukodystrophy, Metachromatic; 10 are open to participants now.

This study's enrollment of 5 is below the median of 22 across 24 interventional studies indexed under Leukodystrophy, Metachromatic.

Browse Leukodystrophy, Metachromatic studies →

Lead sponsor

Institut National de la Santé Et de la Recherche Médicale, France is the lead sponsor of 375 studies on the registry; 82 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Months to 5 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Boys or girls with an early onset form of MLD.
  • Age between 6 months and 5 years, inclusive
  • Diagnostic of MLD based on the measurement of ARSA activity in leukocytes and the accumulation of sulfatides in urine, along with normal activity of at least one other sulfatase
  • Informed consent signed up and willingness for monitoring 2 years after treatment.
  • Normal values for standard laboratory tests

Exclusion criteria

Exclusion Criteria:

  • Absence of ARSA protein by immunocytochemistry and/or ELISA
  • Gestational age \<32 weeks of amenorrhoea and age \< 1 year
  • Brain atrophy with a subdural space > 10 mm in the frontal region
  • Performance IQ\<50 at WPPSI-III or cognitive function \< 3rd percentile at the Bayley's test of infant development
  • If age > 16 months at inclusion, inability to walk few steps alone OR inability to walk few steps with support on one side along with inability to stand up alone
  • Impossibility for anesthesia
  • Malignancy, cardiac malformation, liver dysfunction, or renal dysfunction
  • Neurological disorder, except benign, not related to MLD.
  • Any other clinically significant untreated co-morbid medical condition as determined by the clinical investigator, including cardiac, pulmonary or kidney disease.
  • MRI impossibility
  • Evoked potential impossibility
  • Participation to another therapeutic clinical trial for MLD.
  • Unaffiliated to any French or any other National Health Insurance.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
5 participants (actual)

Study arms

  • Experimental
    AAVrh.10cuARSA

    intracerebral administration of AAVrh.10cuARSA at 12 sites in the white matter of both brain hemispheres.

    Genetic: intracerebral administration of AAVrh.10cuARSA

Interventions

  • Geneticintracerebral administration of AAVrh.10cuARSA
06

What researchers measure

Primary outcomes

  1. Evaluate the tolerance of the intracerebral administration of a single dose of AAVrh.10cuARSA

    Tolerance will be measured by : * Adverse event, * Clinical and neurological exams, * Laboratory tests, * Neuroimagery (CT scan, brain MRI).

    Time frame: During the two years follow-up

Secondary outcomes

  1. Evaluate the efficacy of intracerebral administration of a single dose of AAVrh.10cuARSA to stop the disease progression.

    Efficacy will be measured by: * MLD neurological severity score, * Neurological evaluation, * Motor scores (GMFM, Ashworth and ICARS), * Cognitive functions (Bayley Scales of Infant Development (BSID)(0-42 months), or Wechsler Preschool and Primary Scale of Intelligence-III (WPPSI-III) (43 months-6 years)), * MLD severity MRI score, MRI-DTI parameters, measurement of cerebral atrophy and spectroscopy, * Neuroelectrophysiological tests (peripheral nerve conduction velocity, visual, auditory and somatosensory evoked potentials).

    Time frame: During the two years follow-up

07

Study locations

1 site
  • Bicêtre Hospital - Paris Sud
    Le Kremlin-Bicêtre, France
08

References and documents

Publications

  • Piguet F, Sondhi D, Piraud M, Fouquet F, Hackett NR, Ahouansou O, Vanier MT, Bieche I, Aubourg P, Crystal RG, Cartier N, Sevin C. Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in metachromatic leukodystrophy mice. Hum Gene Ther. 2012 Aug;23(8):903-14. doi: 10.1089/hum.2012.015. Epub 2012 Jul 23. PubMed 22642214 ↗
  • Sondhi D, Johnson L, Purpura K, Monette S, Souweidane MM, Kaplitt MG, Kosofsky B, Yohay K, Ballon D, Dyke J, Kaminksy SM, Hackett NR, Crystal RG. Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis. Hum Gene Ther Methods. 2012 Oct;23(5):324-35. doi: 10.1089/hgtb.2012.120. Epub 2012 Nov 6. PubMed 23131032 ↗
  • Colle MA, Piguet F, Bertrand L, Raoul S, Bieche I, Dubreil L, Sloothaak D, Bouquet C, Moullier P, Aubourg P, Cherel Y, Cartier N, Sevin C. Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate. Hum Mol Genet. 2010 Jan 1;19(1):147-58. doi: 10.1093/hmg/ddp475. PubMed 19837699 ↗
  • i Dali C, Hanson LG, Barton NW, Fogh J, Nair N, Lund AM. Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy. Neurology. 2010 Nov 23;75(21):1896-903. doi: 10.1212/WNL.0b013e3181feb217. PubMed 21098404 ↗
  • Zerah M, Piguet F, Colle MA, Raoul S, Deschamps JY, Deniaud J, Gautier B, Toulgoat F, Bieche I, Laurendeau I, Sondhi D, Souweidane MM, Cartier-Lacave N, Moullier P, Crystal RG, Roujeau T, Sevin C, Aubourg P. Intracerebral Gene Therapy Using AAVrh.10-hARSA Recombinant Vector to Treat Patients with Early-Onset Forms of Metachromatic Leukodystrophy: Preclinical Feasibility and Safety Assessments in Nonhuman Primates. Hum Gene Ther Clin Dev. 2015 Jun;26(2):113-24. doi: 10.1089/humc.2014.139. Epub 2015 Apr 28. PubMed 25758611 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 2, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01801709
Lead sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborators
European Leukodystrophy Association, Assistance Publique - Hôpitaux de Paris
Responsible party
Sponsor
First posted
Mar 1, 2013
Start date
Jun 2014
Primary completion
Jun 2016
Completion
Dec 20, 2022
Last update
Mar 2, 2026

Study contacts

Patrick Aubourg, MD-PhD
principal investigator · Assistance Publique - Hôpitaux de Paris and Institut National de la Santé et de la Recherche Médicale
Caroline Sevin, MD-PhD
study director · Assistance Publique - Hôpitaux de Paris
Michel Zerah, MD, PhD
study director · Assistance Publique - Hôpitaux de Paris
Thomas Roujeau, MD, PhD
study director · Assistance Publique - Hôpitaux de Paris
Nathalie Cartier, MD, PhD
study director · Institut National de la Santé et de la Recherche Biomédicale

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.

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