Gene therapy program
Since 2006, Alliance SANFILIPPO has actively supported a unique gene therapy program for MPS III, contributing 2 million euros in research funding so far. AFM (French Muscular Dystrophy Association) also participates in the funding of this program.
In the past 10 years, considerable progress has been made in the field of gene therapy. Researchers working with MPS III animal models have demonstrated the feasibility of a stable gene transfer within the brain using adeno-associated viruses (AAV) as a vector.
Various studies on MPS IIIA and MPS IIIB in animals have shown sufficient intracranial enzyme distribution which can rectify the main clinical manifestations in mice.
A proposal is under way for a clinical trial using gene therapy for type IIIB due to an alpha-N-acetylglucosaminidase (NaGlu) deficiency (team headed by J.-M. Heard, Institut Pasteur, in Paris and M. Tardieu, Hôpital du Kremlin-Bicêtre).
Alliance SANFILIPPO coordinated discussions between researchers and clinicians susceptible of being interested in developing a similar clinical trial for SANFILIPPO syndrome type IIIA . All of them expressed their desire to work together in exchanging expertise, reagents and preclinical data.
This led to the development of a gene therapy program for intracerebral administration of an adeno-associated virus vector encoding human Sulfamidase. The president of ASF, along with the project managers involved, founded a private law organization, LYSOGENE, to facilitate its promotion and accelerate its realization.
This is a translational research program; its ultimate goal is the medical application of knowledge obtained from basic research, to the benefit of patients.
The program is structured in phases with synergized management of activities and partnerships:
1. Construction and validation of an adeno-associated vector with good brain tropism: a AAV vector (serotype 10) encoding human SGSH and SUMF1 cDNA for treatment of type IIIA SANFILIPPO syndrome.
2. Effectiveness studies carried out on mouse models
3. Vector production according to GMP (Good Manufacturing Practice) quality standards
4. Regulation toxicological studies
5. Preparation of a protocol for open, monocentric phase I/II clinical trials to assess the tolerance of intracerebral administration of this adeno-associated vector to treat type IIIA SANFILIPPO syndrome.
6. Management of regulatory affairs in cooperation with the competent health authorities
7. Study SAF-301 is now authorized by health authorities to be launched (June 2011).
Principal investigator: Dr. Marc TARDIEU, Neuropediatrician,