Launch of the intracerebral gene therapy trial for metachromatic leukodystrophy

Written on Friday 5 April 2013

To families with a child with metachromatic leukodystrophy (MLD)

We are very happy and proud to announce the launch of a new clinical trial for metachromatic leukodystrophy,to which ELA contributed financially (2.4 million euros) and allocated human resources. The trial will be starting to treat several sick children. We would like to thank all the donors trusting us. Every donation made gets us one step closer to find a cure.

The clinical trial “Intracerebral 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 of MLD (TG-MLD)”, lead by Pr Patrick Aubourg (Department of Neuropediatrics and Inserm U986, Bicêtre-Paris Sud hospital, Le Kremlin-Bicêtre, France) as principal investigator, received the authorization from the French Medicine Agency (ANSM) and IRB/IEC to start treating children with early onset forms of MLD.
The disease results from the mutation of the ARSA gene encoding the arylsulfatase A involved in the degradation of sulfatides, a complex lipid present in oligodendrocytes and neurons.. Today, in the early forms of metachromatic leukodystrophy, no treatment can prevent the progression of the disease once the children begin to develop symptoms. The disease causes a rapid decline in intellectual and motor functions..

The objective of the trial is to assess the safety and efficacy of a new experimental drug, AAVrh.10cuARSA, enabling the introduction of the therapeutic ARSA gene directly into the brain using a viral vector based on the Adeno-Associated Virus (the virus is inactivated, cannot become infectious for the treated child, his relatives and friends). Once the vector is injected into the brain, the normal ARSA gene will expressed in brain cells (neurons and myelin forming cells), thereby allowing the production of ARSA enzyme in these cells. The ARSA enzyme can also leave the corrected cells expressing the ARSA gene and correct nearby cells. The vector was produced under pharmaceutical grade proper for a use in humans and under the clinical standards required by the French Medicine Agency (ANSM) and the US Food and Drugs Administration (FDA).

The administration of the viral vector in the brain of the sick children will be performed by a neurosurgical procedure, under general anesthesia, through 6 small holes (of 2 mm) in the skull, to achieve 12 simultaneous deposits of the drug inside the brain. The procedure should not exceed 3 hours. The same mode of administration of a viral vector was recently completed in 4 children suffering from another lysosomal storage disease of the brain. Everything went well and no child developed complications due to the neurosurgical procedure.

Safety and efficacy of the experimental treatment on the cerebral impairment of the children will be assessed for two years. Safety means the absence of adverse events, tolerance to the neurosurgical procedure or tolerance to the viral vector itself. Efficiency is the possibility that this treatment slows the progression of the disease, halts its evolution and even allows recovery of motor impairment or/and cognitive functions. Safety and efficacy will be assessed every 3 months during 2 years during hospitalizations (3-4 days),by clinical and neurological examinations, brain MRI, electrophysiological tests (potentials), and biological tests requiring blood and lumbar puncture.

Five children (boys and girls) between 6 months and 5 years-old could participate to the study if they meet specific inclusion criteria. If older than 16 months, the child should be able to walk alone a few steps, or walk a few steps with assistance on one side. The study will be conducted in 2 hospitals : the Bicêtre Hospital, Paris-Sud, in the department of Pediatric Neurology and at Necker hospital in the Department of Neurosurgery. Families are invited to contact Pr. Patrick Aubourg and Dr. Caroline Sevin, who are responsible for the trial.

Check the study details