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

Plain-language summary

This study examines a gene therapy called AAVrh.10cuARSA delivered into the brain in children with early-onset metachromatic leukodystrophy (MLD). It enrolled children aged 6 months to 5 years diagnosed with MLD based on ARSA enzyme activity and the buildup of sulfatides in urine. The study was carried out in Phase 1/Phase 2 and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Completed

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France

Intervention

intracerebral administration of AAVrh.10cuARSA

Start date

6/1/2014

Estimated completion

12/20/2022

Countries

France

Related genes

Locations

• Le Kremlin-Bicêtre, France

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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:

* 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.