Clinical trials for metachromatic leukodystrophy

Below is the up-to-date information regarding clinical trials for metachromatic leukodystrophy.

Status: Active; Recruitment of patients
Experimental drug: AAVrh10cuARSA viral vector
Objective: To evaluate the tolerance and efficacy of the treatment

Pr. Patrick Aubourg, CHU Bicêtre Paris Sud and Inserm U986, Le Kremlin-Bicêtre, France
Dr. Caroline Sevin, CHU Bicêtre Paris Sud and Inserm U986, Le Kremlin-Bicêtre, France
Dr. Nathalie Cartier-Lacave, Inserm U986, Fontenay-aux-Roses, France
Pr. Michel Zerah, CHU Necker and Inserm U986, Paris, France
Dr. Thomas Roujeau, Hôpital Gui de Chauliac, Montpellier, France

Start date: March 2013
Location: Neuropediatric Department, Bicêtre Hospital Paris Sud, Le Kremlin-Bicêtre, France and Neurosurgery Department (Pr. M. Zerah), CHU Necker, Paris, France
Funding: ELA, PHRC, Inserm
Reference: NCT01801709

5 children with early onset forms of metachromatic leukodystrophy (MLD)

The administration of the viral vector in the brain of the sick children will be performed by  neurosurgical procedure, under general anesthesia, through by 6 small holes (of 2 mm) in the skull, to achieve 12 simultaneous deposits of the drug inside the brain.

Inclusion criteria

  • Boys or girls with an early onset form of MLD.
  • Age between 6 months and 5 years, inclusive
  • Confirmed diagnostic of MLD

Exclusion criteria

  • Specific criteria linked to the form of MLD
  • If older  > 16 months at time of 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
  • Unable to perform  exams  during the trial (MRI, anesthesia, evoked potentials)
  • Any other significant medical condition
  • Participation to another therapeutic clinical trial for MLD


As for the Gene therapy" class="glossy" title="Procedure involving the insertion of a normal gene into an organism in order to achieve a therapeutic objective. This gene (transgene) can be the normal version of a defective gene causing disease or a gene that produces a protein with any therapeutic action." >gene therapy trial in adrenoleukodystrophy, patients are grafted with their own stem cells from bone marrow prior corrected using a lentiviral vector.

Status: Ongoing - Recruitment of patients by invitation
Objective: Evaluation of the safety and efficacy of treatment
Medication: lentiviral vector with the normal human gene ARSA
Reference: NCT01560182

physicians responsible

  • Dr. Alessandra Biffi, Pediatrician at Pediatric Unit of Immunohematology and Bone Marrow Transplantation of HSR.
  • Dr. Maria Sessa, Neurologist in the Department of Neurology at HSR.
  • Dr Attilio Rovelli, Director, Center for Bone Marrow Transplantation in the Department of Pediatrics, San Gerardo Hospital, Monza.
  • Prof. Luigi Naldini, Director of HSR-TIGET
  • Professor Maria Grazia Roncarolo, Director Unit Pediatric Immunohematology and Bone Marrow Transplantation of HSR.


Start of the trial: March 2010
Estimated end of the trial: October 2022
Location: Pediatric Clinical Research Unit of HSR-TIGET & Unit Pediatric Immunohematology and Bone Marrow Transplantation of HSR, Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy.
Sponsor: GlaxoSmithKline
Funding: Italian Telethon Foundation, ELA

20 children with a diagnosis of MLD confirmed by determination of ARSA enzyme activity or by genetic analysis

Forms of the disease concerned:

  • children with late infantile form pre-symptomatic
  • children with early juvenile form pre-symptomatic or within 6 months after the onset of symptoms

  Experimental treatment in 4 phases

  • Removal of bone marrow from the patient and isolation of stem cells to treat;
  • Cell manipulation and gene transfer to cells with the lentiviral vector;
  • Myeloablative therapy the patient (Destruction of the bone marrow);
  • Reinjection engineered cells to the patient (autologous).

Source :

Consultez les résultats intermédiaires de l'essai (pages 6-7)

This study is to provide every 2 weeks the normal ARSA enzyme in human cerebrospinal fluid of children with metachromatic leukodystrophy.

Status: Ongoing - Recruitment of patients ended

Type of study: Phase I / II multicenter, open, with ascending doses of drug

Medicine: HGT-1110, human ARSA enzyme formulation normal intrathecal injection.

Reference: NCT01510028

Objective: To determine the safety of doses ascendantes de HGT-1110 administered by intrathecal injection for 38 weeks in children with metachromatic leukodystrophy.

Area of trying

  • University Hospital of Copenhagen, Copenhagen, Denmark
  • Bicetre Hospital, Le Kremlin-Bicetre, France
  • Universitats-Kinderklinik, Tubingen, Baden-Wuerttemberg, Germany

Study Director: Dr. Eric Crombez, Shire Human Genetic Therapies, Inc..

Physicians responsible

  • Dr. Christine Dali, Department of Clinical Genetics, Juliane Marie Centre, University Hospital of Copenhagen, Copenhagen, Denmark
  • Dr. Caroline Sevin, Department of Pediatric Neurology, Bicetre Hospital, Le Kremlin-Bicetre, France
  • Dr. Joachim Riethmuller, Center for Pediatric Clinical Studies, Universitats-Kinderklinik, Tubingen, Baden-Wuerttemberg, Germany

Beginning of the study in September 2012

Estimated study completion: March 2015

Sponsor: Shire Human Genetic Therapies, Inc.


Maximum 18 patients participating in the trial. All receive treatment HGT-1110. Boys and girls are eligible.

Inclusion criteria

  • Diagnosis of metachromatic leukodystrophy confirmed both by a deficiency of arylsulfatase A as measured by the test on white blood cells and urinary sulfatides high
  • The first symptoms of the disease at the age of 30 months or earlier.
  • Being ambulatory at the time of patient selection (ability to walk 10 steps with one hand held).
  • The patient must be less than 12 years old.
  • Present metachromatic leukodystrophy neurological signs at the time of patient selection.
  • The patient and his parents or guardians must satisfy the constraints of the clinical protocol.
  • Parents or legal guardians of the patient must sign a letter of consent before inclusion.

Exclusion criteria

  • History of bone marrow transplantation.
  • Known or suspected hypersensitivity to anesthesia or high risk for anesthesia in case of problems with respiratory or other medical problems.
  • Other medical problem or serious illness.
  • The patient is participating in another clinical trial within 30 days prior to consideration for inclusion in the study.
  • The patient is pregnant or breastfeeding.
  • The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including:
    • The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
    • The patient's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator.
    • The patient has a known or suspected local or general infection.
    • The patient is at risk of abnormal bleeding due to a medical condition or therapy.
    • The patient has one or more spinal abnormalities that could complicate safe implantation or fixation.
    • The patient has a functioning CSF shunt device.
    • The patient has shown an intolerance to an implanted device

Experimental treatment (3 groups)

  • Group 1: 6 patients treated for 38 weeks with 10 mg of HGT-1110 every 2 weeks by intrathecal injection via a specific device.
  • Group 2: 6 patients treated for 38 weeks with 30 mg of HGT-1110 every 2 weeks by intrathecal injection via a specific device.
  • Group 3: 6 patients treated for 38 weeks with 100 mg of HGT-1110 every 2 weeks by intrathecal injection via a specific device.

Evaluation Criteria

Primary criteria: Safety of the administration of HGT-1110 intrathecal

Secondary endpoints

  • Effect of the administration of HGT-1110 intrathecally on motor function
  • Pharmacokinetic profile of HGT-1110 in serum after administration of a single dose or repeated doses
  • Concentrations of HGT-1110 in the cerebrospinal fluid before each intrathecal administration

Patients who participated in the study through week 40 can be invited to participate to the extension study (Referenced NCT01887938) which goal is to evaluate long-term safety and efficacy of intrathecal administration of HGT-1110 in patients with metachromatic leukodystrophy.


Status: Ongoing - Recruitment of patients
Objective: To study the progression of cerebral MLD by new techniques and MRI abnormalities correlate with tests assessing motor and intellectual function of the patient.

Principal investigators

  • Professor Patrick Aubourg, Department of Pediatric Neurology, Bicêtre Hospital, Le Kremlin-Bicetre, France
  • Dr Caroline Sevin, Pediatric Neurology Department, Hôpital Bicêtre, Le Kremlin-Bicetre, France
  • Dr. Lucie Hertz-Pannier, Biomedical Research Unit, Neurospin, Gif-sur-Yvette, France
  • Dr Laurence Lecomte, Necker Hospital, Paris, France

Location : Bicêtre Hospital, Le Kremlin-Bicetre & Neurospin, Gif-sur-Yvette, France
Start date: September 2010
Duration of the study: 6 months for MLD patients; 12 months for controls
Funding: AP-HP, ELA
Reference: NCT01325025


  • 10 children between 1-6 years with a diagnosis of metachromatic leukodystrophy less than 18 months.
  • 25 controls

Experimental design
2 visits are scheduled:

  • Visit 1: MRI and evaluation of motor and cognitive functions
  • Visit 2 (6 months after visit 1 for MLD patients; 12 months after visit 1 for controls): MRI and evaluation of motor and cognitive functions

Its duration does not exceed 60 minutes. The child must be fasting at least 3 hours before the exam. To ensure the immobility of the child during the examination, a sedative, chloral hydrate, it is administered orally or rectally. After the examination, the child will remain supervised on site 1-2h before departure.

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