Final Report Summary - NEUROPROMISE (Neuroprotective strategies for multiple sclerosis)
NEUROPROMISE was established in 2005 as an Integrated Project under the 'Life sciences, genomics and biotechnology for health' Thematic Priority Area of the Sixth Framework Programme.
The purpose of the consortium was to investigate in depth the genetic and mechanistic pathways involved in multiple sclerosis (MS), the most common chronic inflammatory disease of the central nervous system, and exploit this knowledge for the development of better therapeutic agents. With its 19 academic and 3 industrial partners, the project combined expertise in the fields of neurodegenerative diseases, human and animal genetics, molecular and cellular neuroscience, neuropathology, neuroimmunology, electrophysiology, proteomics, genomics, in vivo disease models, biotechnology of recombinant proteins, antibody production and nanotechnologies.
The results of the genetic studies carried out in the subproject 'Identification' are one of the most relevant deliverables of NEUROPROMISE. The comparative genetic approach in rodent platforms and MS patient-control cohorts together with validation studies of MS risk genes identified in genome-wide association analyses has greatly contributed to widen our understanding of the contribution of genes outside the major histocompatibility complex (MHC) locus (the main known determinant of MS genetic susceptibility) to disease development. Despite the low impact of individual non-MHC genes in determining MS risk, a better understanding of the pathways they are involved in is starting to provide new insights into the complex mechanisms involved in MS pathogenesis.
It is now widely accepted that axon injury and degeneration is a significant component of MS pathology and that loss of axons underpins the irreversible progression of the neurological deficits. Knowledge of the molecular mechanisms underlying axon degeneration is therefore critical to design rational neuroprotective therapies for MS. Within NEUROPROMISE, transcriptomics and proteomics approaches have been used to identify the early molecular changes occurring in axonal projections of defined neuronal populations as well as in whole brain tissue in different experimental models of neuroinflammation and neurodegeneration. Patterns of transcripts and proteins identified using these approaches were subjected to extensive bioinformatic analysis and validated using appropriate techniques. Furthermore, specific mechanisms of inflammatory neurodegeneration were investigated in post-mortem brain tissue from MS patients and in experimental models.
The results of the NEUROPROMISE project have significantly advanced our understanding of MS and of neuroinflammatory processes in general. With the knowledge acquired on genes and mechanisms involved in inflammatory neurodegeneration and neuroprotection and with the compounds developed on the basis of this knowledge, more reliable models of MS pathogenesis have been proposed and candidate therapeutic molecules have been developed and will be proposed for subsequent clinical evaluation.
The purpose of the consortium was to investigate in depth the genetic and mechanistic pathways involved in multiple sclerosis (MS), the most common chronic inflammatory disease of the central nervous system, and exploit this knowledge for the development of better therapeutic agents. With its 19 academic and 3 industrial partners, the project combined expertise in the fields of neurodegenerative diseases, human and animal genetics, molecular and cellular neuroscience, neuropathology, neuroimmunology, electrophysiology, proteomics, genomics, in vivo disease models, biotechnology of recombinant proteins, antibody production and nanotechnologies.
The results of the genetic studies carried out in the subproject 'Identification' are one of the most relevant deliverables of NEUROPROMISE. The comparative genetic approach in rodent platforms and MS patient-control cohorts together with validation studies of MS risk genes identified in genome-wide association analyses has greatly contributed to widen our understanding of the contribution of genes outside the major histocompatibility complex (MHC) locus (the main known determinant of MS genetic susceptibility) to disease development. Despite the low impact of individual non-MHC genes in determining MS risk, a better understanding of the pathways they are involved in is starting to provide new insights into the complex mechanisms involved in MS pathogenesis.
It is now widely accepted that axon injury and degeneration is a significant component of MS pathology and that loss of axons underpins the irreversible progression of the neurological deficits. Knowledge of the molecular mechanisms underlying axon degeneration is therefore critical to design rational neuroprotective therapies for MS. Within NEUROPROMISE, transcriptomics and proteomics approaches have been used to identify the early molecular changes occurring in axonal projections of defined neuronal populations as well as in whole brain tissue in different experimental models of neuroinflammation and neurodegeneration. Patterns of transcripts and proteins identified using these approaches were subjected to extensive bioinformatic analysis and validated using appropriate techniques. Furthermore, specific mechanisms of inflammatory neurodegeneration were investigated in post-mortem brain tissue from MS patients and in experimental models.
The results of the NEUROPROMISE project have significantly advanced our understanding of MS and of neuroinflammatory processes in general. With the knowledge acquired on genes and mechanisms involved in inflammatory neurodegeneration and neuroprotection and with the compounds developed on the basis of this knowledge, more reliable models of MS pathogenesis have been proposed and candidate therapeutic molecules have been developed and will be proposed for subsequent clinical evaluation.
