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6.1. Genomic signature-based small molecule screening of neural stem cells to identify novel compounds to enhance oligodendrogenesis
Lead scientist: Carme Costa
Genomic signatures will be defined in the different stages of differentiation from neural stem cells to mature oligodendrocyte. The signatures will be used to identify new drugs that could induce oligodendrogenesis. In vitro validation will be performed to confirm that the addition of these compounds to cells under different stages of lineage commitment produces the desired gene expression signature. The selected compounds will be finally tested in vivo, in an experimental autoimmune encephalomyelitis mouse model.
6.2. DNA vaccination as a therapy of multiple sclerosis
Lead scientist: Nicolás Fissolo
To evaluate the potential of DNA vaccines as a possible treatment of MS, plasmid vectors expressing auto-antigens involved in the disease will be created and tested in experimental autoimmune encephalomyelitis, the animal model of MS.
6.3. Tolerance induction in experimental autoimmune encephalomyelitis using gene therapy
Lead scientists: Jordi Barquinero and Carmen Espejo
Previous collaboration works with the group of Gene and Cell Therapy of our institution resulted in the development of a therapeutic strategy in which bone marrow cells were genetically modified to express a self-antigen with the aim to induce antigen-specific tolerance. We could see a therapeutic effect even in the absence of myeloablation, thus suggesting that a concrete population of cells generated in the cell culture, but not cells with a repopulating capacity, were responsible for the therapeutic effect seen in these mice. We have identified a candidate population, called myeloid derived suppressor cells that might be mediating the antigen-specific effect.
6.4. Role of the heat shock protein (HSP)-70 in the pathogenesis of multiple sclerosis
Lead scientist: Carmen Espejo
By means of interfering RNA, we are studying whether silencing HSP-70 expression changes the level of protection of the cells from the central nervous system in front of stimulus like the inflammation typical of MS.
6.5 Role of semaphorins 3A and 7A in neuroregeneration and immune regulation in EAE model
Lead scientist: Carmen Espejo
This project aims to study the role of semaphorin 3A (sema3A) and sema7A, two axonal guidance molecules also involved in the regulation of immune responses, in experimental autoimmune encephalomyelitis (EAE) pathogenesis as well as their therapeutic implications.
6.6. Inhibition of Delta-like ligand-4 as a therapy in a murine model of multiple sclerosis
Lead scientist: Herena Eixarch
Delta-like ligand-4 (Dll4) is one of the ligands for Notch, which has been specifically implicated in the differentiation of Th1 T-cells and may have a role in the development of Th17 immune responses. Taking into account that Th17 responses are directly involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS), our hypothesis is that the inhibition of Dll4 could have a beneficial effect on a MOG-induced EAE model.
6.7. TNF signaling pathway in multiple sclerosis
Lead scientist: Luís Agulló
This project has 3 main objectives: first, to find changes in the immune response resulting from TNFRSF1A polymorphisms, what could allow the development of specific treatments for these patients in the future, second, to evaluate in animal models the selective blockade of type 1 and 2 receptors of TNF by siRNA as a potential therapy in EM, and, finally, to propose pharmacophores that interact selectively with TNF receptors 1 or 2 and that could be the structural base for the development of new drugs.
6.7. Intrathecal IgM and IgG synthesis in experimental autoimmune encephalomyelitis
Lead scientist: Carmen Espejo
Experimental autoimmune encephalomyelitis (EAE) is an inducible demyelinating disease serving as animal model for multiple sclerosis (MS). Both Cerebrospinal fluid (CSF)-restricted oligoclonal IgG and IgM bands are detectable in MS patients. In addition, IgG oligoclonal bands are used as a paraclinical tool to help in MS diagnosis.
We aim to study intrathecal IgG and IgM synthesis over time in EAE model.
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