The AgedBrainSYSBIO project on systems biology of synapse proteins and aging was officially launched March 18 in Paris. The European collaborative research project is funded by the European Commission under the Health Work Program of the Seventh Framework Program.

To address aging issues, such as cognitive decline and Alzheimer’s disease, the European Commission-funded research effort is crucial as there are still no curative drugs, with only symptomatic treatment able to delay the disease progression.

Over the last years, Genome-Wide Association Studies (GWAS) have been instrumental to identify genes that mediate genetic risk associated to Late-Onset Alzheimer Diseases (LOAD). These approaches based on the genetic comparison of large cohorts of patients and healthy aged persons, and for which three academic partners have been involved (Inserm U894; Institut Pasteur Lille, University of Antwerpen), have been largely funded by Europe. Additionally, a variety of new sets of data have been built and have delivered the state-of-the art of protein-protein interactions, their localization in subregions of human neurons and genome-wide transcriptome analysis of human neurons derived from aged patient fibroblasts. So far however, in spite of a huge amount of data available and existing in vitro and in vivo models, these approaches have not been successfully translated into the clinic separately.

The AgedBrainSYSBIO will take advantage of these large set of data, will cross them to other large-scale aging databases and will include all of these know-how, technologies and results. Thanks to the involvement of four European SMEs, this program is expected to get results readily translated into preclinical studies.

AgedBrainSYSBIO project assembles 13 well-established research teams both from academia and industry. The scientists will share results and know how on LOAD GWAS gene discovery, comparative functional genomics in mouse and drosophila models, in mouse transgenic approaches research on human induced pluripotent stem cells (hiPSC) and their differentiation in vitro and modeling pathways with emphasis on comparative and evolutionary aspects. Importantly, the four European SMEs involved will bring their complementary expertise. Quretec (Estonia) will be a key partner for data management solutions and bioinformatics data analyses; Hybrigenics (France) brings experience in comparative proteomics and protein-protein interaction analyses; Genebridges (Germany) is marketing novel strategies for DNA engineering in mammalian cells; reMynd (Belgium) develops protein misfolding-modifying treatments against LOAD .

Together, researchers will address the basis of brain aging by studying the pathways involved in LOAD combining integrative systems biology and comparative genomics. One of the first steps will be to identify the interactions through which the ageing phenotype develops in normal and in disease conditions; on this basis, novel pathways and their evolutionary properties will be modeled and experimentally tested in order to identify druggable targets. This work will finally allow the validation of new druggable targets and markers as a proof-of-concept towards the prevention and cure of aging cognitive defects.

“This ambitious project integrates the numerous European initiatives, such as JPND, as well as national research programs, which address the scientific and societal challenge of neurodegenerative diseases,” said Michel Simonneau, MD, PhD, professor at Ecole Normale Supérieure de Cachan, who coordinated this effort. “This project receives the decisive input of four small to medium-size enterprises (SMEs) that allow us to get candidate solutions for curing and preventing common age-related diseases. The links between academia and industry is the driving force of this work program and in the end will hopefully benefit to all of us."