Research is conducted by the laboratory directed by Daniel Scherman (Inserm U640/CNRS UMR 8151, Faculté de Sciences Pharmaceutiques et Biologiques), and funded by Alliance SANFILIPPO and Inserm.  It is exploring two complementary avenues.

The laboratory first focused on physiopathological studies in order to identify new markers in the neurodegeneration process described for SANFILIPPO syndrome.  The relation between the abnormal storage of glycosaminoglycans (GAGs) and neurological deterioration is still not well understood.  However, as previously demonstrated in several neurological lysosomal disorders, inflammatory molecules may be involved.  Therefore, researchers compared gene expression profiles in cerebral tissue from normal and MPS IIIA mice, focusing on inflammation and apoptosis-related genes (apoptosis is a process of programmed cell death).
The profile was evaluated in different regions of the brain throughout the animals’ lives.  New markers for SANFILIPPO syndrome were thus identified.  They could easily be used in preclinical studies to monitor neurological deterioration.

The second avenue, explored conjointly, consists in testing several anti-inflammatory and anti-oxidant molecules, alone or in combination, on MPS III mouse models in order to determine which are the most capable of restricting the neuroinflammatory process, triggering possible improvements in the animals’ condition.  Various biochemical and histopathological techniques have been used to analyze inflammation reduction.

The research team includes Daniel Scherman (laboratory director and project manager), Audrey Arfi and Magali Richard (researchers).

The results of this study were presented recently (June 2010) in Adelaide, Australia, as part of the 11th International Symposium on Mucopolysaccharide and Related Diseases.

They are now published:

Arfi A, Richard M, Gandolphe C, Bonnefont-Rousselot D, Thérond P, Scherman D. Neuroinflammatory and oxidative stress phenomena in MPS IIIA mouse model: The positive effect of long-term aspirin treatment. Mol Genet Metab. 2011 Feb 3.[Epub ahead of print]