Successful gene therapy for three children suffering from metachromatic leukodystrophy

Written on Monday 12 May 2014

The ELA association is extremely happy to announce a new medical success for leukodystrophies. The first results of 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 for metachromatic leukodystrophy (MLD) carried out by Dr. Alessandra Biffi and Pr. Luigi Naldini from the TIGET San Raffaele Institute in Milan (Italy) have just been published in the prestigious Science journal. Three children were treated and their disease progression was halted. Three years after treatment they are well. For the first time this therapy offers hope of treatment to patients suffering from MLD.

Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disease wherein a genetic defect leads to a rapid demyelination of the nervous system, for which no treatment exists. Children suffering from its severe form rapidly lose their motor and cognitive capacities, until early death occurs.

To correct the MLD genetic defect, doctors have removed stem cells from the bone marrow of the patient, corrected them by introducing the normal gene with the help of a lentiviral  vector derived from the inactivated AIDS virus, then re-injected them into the patient.

This experimental treatment is based on the gene therapy for adrenoleukodystrophy described in 2009 and funded by ELA that opened treatment perspectives for other rare diseases or even more frequent ones.

“The therapeutic mechanism is more sophisticated”, precises Alessandra Biffi, responsible for the trial, “the corrected cells reach the brain by the sanguine pathway and release the correct protein that is recovered by the surrounding neurons.”

Eugenio Montini, coordinator of molecular analyses, indicates “to date, we have never seen an approach manipulating stem cells by gene therapy that is equally efficient and safe“.

Gene therapy allowed us to obtain extensive and stable gene replacement adds Dr. Biffi, “which led to an increased expression of the protein in stem cells and in the cerebrospinal fluid. Seven to twenty one months after the predicted age for the apparition of symptoms, the disease had not broken out or had not progressed in the three patients treated”.

The published results only refer to the treated children for whom there is sufficient perspective. Five other patients have been treated in the meantime.

Three years after the beginning of the clinical trial, the results obtained are very encouraging: the therapy is not only safe, but is also effective and capable of changing the clinical history of these severe diseases. After 15 years of efforts, of success in the laboratory but also of frustration, it is very exciting to be able to bring a concrete solution to the first patients”, states Pr.  Naldini, head of TIGET.

We hope to extend this treatment to all children suffering from the pre-symptomatic stage of late infantile MLD” explains Alessandra Biffi. “It will take several years before such a treatment can be offered to the community of MLD sufferers“.

Pr. Naldini also describes the success of gene therapy against the Wiskott-Aldrich syndrome, an immune deficiency that makes children vulnerable to infections.

Guy Alba, founding president of ELA, is obviously delighted by this new success that reinforces the work carried out by the association over the last 20 plus years concerning research into leukodystrophies: “We are proud to have participated in the funding of this trial. It falls within the extension of an initial success in 2009 by two French groups: Aubourg & Cartier (of St Vincent de Paul), and Fischer & Cavazzana-Calvo (of Necker) working on gene therapy against adrenoleukodystrophy (ALD). We are sharing this promising result with all the families concerned and with the contributors who have enabled us to be the principal sponsor (over 7.5M€ given to research into ALD). We are also financing a new gene therapy trial for MLD by intracerebral injection carried out this year at the Bicêtre Hospital by Dr. Caroline Sevin and Pr. Aubourg. All these initiatives fit into the strong desire of the ELA association to give priority to clinical trials in the closest interests of the patients. Effectively, since 1992 ELA is the greatest financer of research into leukodystrophies.


Key Figures

With 34.5 million euros invested and 434 research programs, ELA is the first backer of research into leukodystrophies

Financial contribution of ELA to the Milan MLD gene therapy trial: 300,000 €

Since its creation ELA has devoted over 4.1 M€ to research into metachromatic leukodystrophy (of which 3.2M€ has been affected to the new gene therapy trial by intracerebral injection)

Metachromatic leukodystrophy represents 16% of patients inventoried by the association


For more information about this clinical trial