Séverine Fruchon
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Project:
Targeting and rehabilitation of inflammatory macrophages by phosphorus dendrimers: therapeutic perspective for chronic inflammatory diseases
Since 2003, in collaboration with the group of Dr. Caminade (Laboratoire de Chimie de Coordination, Toulouse), we have discovered, documented and patented the anti-inflammatory and immunomodulatory properties of a synthetic molecule (a phosphorus dendrimer, named ABP), toward monocytes / macrophages (myeloid cells). We have demonstrated in a previous work that ABP dendrimer polarize human monocytes to an M2 anti-inflammatory phenotype (Fruchon S, 2009). This allowed us to consider ABP as an innovative nano-molecule for the treatment of uncontrolled inflammatory processes. Since then, this molecule has shown remarkable in vivo efficacy in murine models of arthritis (Hayder M, 2011) and Experimental Autoimmune Encephalomyelitis (collaboration with the team of Pr. Roland Liblau, CPTP, Hayder M, 2015), which are models of Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS), respectively. Moreover, we have documented the property of ABP to dampen acute inflammation (Fruchon S, 2013). Finally, we have demonstrated in a preclinical safety study, that macaques tolerate well repeated injections of ABP dendrimer, since no adverse effects were observed (Fruchon S, 2015). All together, these results provide preclinical Proofs of Concept of the therapeutic efficacy and safety of the dendrimer. We do believe that microglia, myeloid cells of the brain, could be impacted by the ABP dendrimer, as monocytes/macrophages in the periphery. Thus, ABP appears as an innovative drug candidate for the treatment of chronic inflammatory diseases, including those of the CNS.
Targeting and rehabilitation of inflammatory macrophages by phosphorus dendrimers: therapeutic perspective for chronic inflammatory diseases
Since 2003, in collaboration with the group of Dr. Caminade (Laboratoire de Chimie de Coordination, Toulouse), we have discovered, documented and patented the anti-inflammatory and immunomodulatory properties of a synthetic molecule (a phosphorus dendrimer, named ABP), toward monocytes / macrophages (myeloid cells). We have demonstrated in a previous work that ABP dendrimer polarize human monocytes to an M2 anti-inflammatory phenotype (Fruchon S, 2009). This allowed us to consider ABP as an innovative nano-molecule for the treatment of uncontrolled inflammatory processes. Since then, this molecule has shown remarkable in vivo efficacy in murine models of arthritis (Hayder M, 2011) and Experimental Autoimmune Encephalomyelitis (collaboration with the team of Pr. Roland Liblau, CPTP, Hayder M, 2015), which are models of Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS), respectively. Moreover, we have documented the property of ABP to dampen acute inflammation (Fruchon S, 2013). Finally, we have demonstrated in a preclinical safety study, that macaques tolerate well repeated injections of ABP dendrimer, since no adverse effects were observed (Fruchon S, 2015). All together, these results provide preclinical Proofs of Concept of the therapeutic efficacy and safety of the dendrimer. We do believe that microglia, myeloid cells of the brain, could be impacted by the ABP dendrimer, as monocytes/macrophages in the periphery. Thus, ABP appears as an innovative drug candidate for the treatment of chronic inflammatory diseases, including those of the CNS.
Animal and Cellular models:
- Culture of PBMC
- Isolation of primary human monocytes
- Culture of BV2 cells (murine microglial cell line)
- Isolation of primary microglial cell from adult mouse brain
- Culture of PBMC
- Isolation of primary human monocytes
- Culture of BV2 cells (murine microglial cell line)
- Isolation of primary microglial cell from adult mouse brain
Techniques and Methods: