Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome

Protocol AMT110-CD-001: A Phase I/II, Open-label, Study of Intracerebral Administration of Adeno-associated Viral Vector Containing the Human Alpha-N-acetylglucosaminidase cDNA in Children With Sanfilippo Type B Syndrome

This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.

This is an open-label, phase I/II study of intra-cerebral administration of adenovirus-associated viral vector containing the human NAGLU cDNA to children suffering from Sanfilippo type B syndrome.

Four patients, 18 months up to the 5th birthday, have been included.

The inclusion period will be 8 to 12 months. The duration of follow-up for each patient is 1 year post-surgery. The duration of the first extension phase is 18 months. The duration of the second extension phase is 36 months. Therefore, the maximum time of the follow-up will be 66 months

Inclusion criteria:

• Age: 18 months up to 60 months (5th birthday);
• Onset of clinical manifestations related to mucopolysaccharidosis type IIIB (MPSIIIB);
• NAGLU activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls;
• Patient affiliated to, or covered by a French social security regimen, or European patients with European Health Insurance Card;
• Family understanding the procedure and the informed consent;
• Signed informed consent by both parents or legal representative;
• Vital laboratory parameters within normal range.

Exclusion Criteria:

• Presence of brain atrophy on baseline MRI judged on a cortico-dural distance of more than 0.6 cm;
• Any condition that would contraindicate general anesthesia;
• Any other permanent medical condition not related to MPSIIIB that could contraindicate the study participation;
• No independent walking (ability to walk without help);
• Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection (sleep and mood regulators are accepted);
• Any condition that would contraindicate treatment with Modigraf®, Cellcept® and prednisolone (Solupred® and Solumedrol®).