In March 2010, a clinical trial based on the transplantation of autologous hematopoietic stem cells modified with a drug vector encoding normal human arylsulfatase A (ARSA) was authorised by the Italian authorities. The clinical protocol includes patients suffering from the form late infantile (TI) and early juvenile (JP), in the pre-symptomatic stage and, for patients with the JP form, in the pre-symptomatic and early symptomatic stage, as this patient profile should provide a reasonable perspective in terms of clinical benefit.

The objectives of the study are to assess the safety and efficacy of the treatment by monitoring any side effects and by measuring the scientific workshops of the patients’ motor and cognitive abilities as well as the demyelination of the nervous system.

Recruitment for the study is now complete, with twenty patients included (of which nineteen were treated). Ten of these patients had a biochemical, molecular and family history consistent with a diagnosis of MLD IT and ten others had a clinical and / or family history consistent with the JP form of the disease.

Preliminary data indicates that, overall, the transplant procedure was followed by good bone marrow recovery with no unexpected short to medium term side effects. In addition, reconstitution of ARSA activity is observed in the reconstituted blood cells and in the cerebrospinal fluid of patients.

For patients with the IT form for whom we have an informative follow-up (observation of at least 1.5 years after gene therapy [TG]), we report preliminary evidence of a therapeutic benefit associated with the procedure.

Indeed, the clinical state, the motor and cognitive capacities and the myelination of the central nervous system of these children are very clearly superior to the expected damage given the known evolution of the disease from which they suffer, their age, and the course of the illness of their affected older brother or sister.

The magnitude of the observed benefits may be influenced by the time interval between TG and expected onset of illness.

Two patients with the IT form treated shortly before the onset of the illness or at the time of onset showed some first signs of illness within 6-12 months of TG and were then stabilised.

Patients treated long enough before symptoms appear show virtually no clinical signs of the disease, have habitual motor and cognitive development, and enjoy a normal quality of life for their age. We are not yet sure whether TG can protect children with the IT form of the disease from peripheral demyelination.

Observation of patients with the JP form treated to date does not yet allow conclusions to be drawn in terms of therapeutic benefit since their disease was at a different stage at the time of treatment and due to short follow-up.

These data is  generally very encouraging, but will need to be confirmed by continued long-term monitoring.

We are currently studying with the pharmaceutical company GSK, one of our partners in this research, the Italian Telethon Foundation and the San Raffaele Hospital, the possibility of carrying out an appropriate program, in accordance with the Italian legislation, which would allow other children  suffering from MLD to receive this treatment, although it has not yet received a marketing authorisation. Various points will have to be discussed before being able to propose such a programme. In particular, it will be necessary to determine whether the preliminary data from this study allows us to have a favourable benefit / risk balance in order to be able to offer this treatment to children outside the framework of a clinical trial.

If authorised, this experimental treatment will not be generalised, and this therapeutic approach will have to be evaluated for each patient.