NOVEL IMMUNOTHERAPIES IN CHRONIC NEUROLOGICAL DISEASES - REDUCING PATHOGENESIS AND IMPROVING HEALING
Swedish Research Council
In Multiple Sclerosis, Glioblastoma multiformes and Alzheimers Disease we hypothesise that disease chronicity is due to dysregulation of immunological mechanisms associated with macrophage/microglia (Mf/mG) activation in the CNS. Our research program aims to develop novel immunotherapies for treatment of these neurological diseases, and we use a multifaceted approach with myeloid cell therapy, vaccination and tolerance induction. We developed a myeloid cell therapy concept based on injection of specifically in vitro re-programmed Mf/mG in order to reset the immunological balance in vivo. Our focus in MS is to study healing of the damaged tissues, specific effects on both regulatory T cell function and neural stem cell development within the affected tissues. Combining immunomodulatory/regenerative therapies will be tested in chronic MS models. Our data demonstrate that transfer of pro-inflammatory activated Mf can cure mice of GBM and we will expand on this by refining the treatment and characterising the immunological mechanisms operating within the tumour environment. We test a novel CNS targeting strategy involving intra-arterial delivery of Mf/mG that circumvents the requirement of surgically opening the skull. In AD we will test the therapeutic effects of adoptive cell transfer of Mf/mG in amyloid and Tau models and use specific Mf/uG transient depletion in the CNS and blood to investigate the relative roles of these cell populations in pathogenic and healing responses.