Jean-Chretien Norreel

Pharmaxon is a French biotechnology company focused on the development of novel drugs to treat serious neurological disorders. Pharmaxon was incorporated in 2004 and is a spin-off of the Developmental Biology Institute of Marseilles. The company is devoted to search and develop new drugs that target severe pathologies or traumas of the Central Nervous System.
Pharmaxon is currently developing compounds in 3 therapeutic areas: spinal cord injury, mild cognitive impairment and gliomas. Pharmaxon has also a recognized expertise in the modulation adhesive molecules involved in numerous aspects of neuroplasticity. We have thus discovered and caracterized mimotope peptides of the glycoprotein PSA-NCAM which is highly expressed in the developing and the injured central nervous system. By mimicking PSA-NCAM, we aim at enhancing neuroplasticity. Pharmaxon has also a recognized expertise in testing the potential efficacy of compounds in various spinal cord injury animal models. We have also showed that this mimetic peptide showed a strong pro-mnexis effect when injected in the hippocampus.

To date, therapies to treat spinal cord injury have not been successfully due to their lack at overcoming critical molecular and cellular consequences of spinal cord trauma. Medications to effectively treat SCI must be able to overcome number of problems to promote reconnection of neurons from the spinal cord for functional recovery. Indeed, a glial scar forms at the site of injury that creates an effective barrier for neuronal re-growth. One role of this scar is to seclude the injury site from healthy tissue, preventing a cascade of tissue damage to occur. The benefit of glial scarring to the overall survival of the patient comes at the expense of the ability for long-distance functional regeneration (Silver & Miller, 2004). There are two possible ways to increase neuronal regeneration after spinal cord injury: one is to prevent the damaged neurons to answer to the inhibitory signal coming out from the scar, the other is to reduce the formation of this scar. Since screening a large number of molecules on animal models is heavy and costly, we have developed various cell assays that mimic what happens in humans. Several hundred of molecules are screened in these tests and drugs with positive effect are selected and further analyzed in secondary in vitro assays and animal models of spinal cord injury.

Training and transfer of knowledge environment
PHARMAXON is linked to the Marseille Developmental Biology Institute (IBDML) and students are trained in collaboration with the University of Aix-Marseille and are following the regular training programme of the Graduate School .

Jean-Chretien NORREEL    COO    Axon regeneration, Myelination, Spinal Cord Injury in vitro and in vivo models
Isabelle BOQUET    In vitro group leader    Glial Scar, Axon regeneration, High Content Screening
Annelise VIALLAT    In vivo group leader    Axon regeneration, CNS traumas in vivo models
Dorothée BUTTIGIEG    In vitro project leader    Glial Scar, Axon regeneration, High Content Screening
Coralie GIRIBONE    In vivo project leader    CNS traumas in vivo models

Relevant publications

1. Florian C, Foltz J, Norreel JC, Rougon G, Roullet P (2006) Post-training inhippocampal injection of synthetic poly-alpha-2,8-sialic acid neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice. Learn Mem. 13: 465-72
2. Passage E*, Norreel JC*, Noack-Fraissignes P, Sanguedolce V, Pizant J, Robaglia-Schlupp A, Pellissier JF, Fontes M. (2004) Ascorbic acid treatment corrects the Charcot-Marie-Tooth phenotype. Nature Medecine, Published online 21 March 2004. * the first two authors equally contributed to the work
3. Norreel JC,  Pflieger JF, Pearlstein E, Simeoni-Alias J, Clarac F, Vinay L. (2003) Reversible disorganization of the locomotor pattern after neonatal spinal cord transection in the rat. Journal of Neuroscience, 23 : 1924 – 32