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Investigation on hybrid molecules as powerful novel therapeutic approaches for Multiple Sclerosis and myelin- related rare diseases

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS): Molecular Etiology and Novel Treatments

Senior Researcher : Fernando de Castro Soubriet

Research Centre or Institution : Instituto Cajal. CSIC. Madrid.


Multiple Sclerosis (MS) is a neurodegenerative and autoimmune disease. It represents the main primary demyelinating disease, it is chronic and severe, affecting mainly women and debuting normally in young adults, which gives rise to important medical and social consequences to patients, their families and national health systems. Parallely there is a substantial number of primary demyelinating diseases affecting the CNS, collectively known as leukodystrophies and classified as rare diseases.

Current pharmacological strategies for MS are based on immunemodulators: these affect the progress of the disease but are not curative. Subsequently new therapeutic strategies are required in order to improve the prognosis and evolution of myelin-related diseases.

In this project we will explore the advantages of hybrid molecules composed of a small molecule and a peptide to increase the accuracy in the delivery of candidate drugs. Anti- NG2 peptides (NG2p) are small aminoacidic chains that specifically recognize the NG2 receptor, which is differentially expressed in oligodendrocyte precursor cells (OPCs) and serve to characterise this cell population. The small molecule VP3.15 has showed promising properties as a trigger of oligodendrogliogenesis in human OPCs cultures. The effect of NG2p-VP3.15 and other hybrids will be assessed in cell culture assays and in vivo animal models of MS (murine EAE) and one leukodystrophy model. The expected outcome of this project is to find a powerful candidate with improved pharmacological properties against demyelinating diseases, while deepening our understanding of their underlying biological mechanisms. In a final stage, patenting or licensing any possible hits would have an ulterior impact as a technology transfer outcome.

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