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

19th national competition for scientific and technical research

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.

Abstract

In these few months since the beginning of the project our, group together with the group of Dr. Valle Palomo at CIB-CSIC, has set out the following work pipelines:

Test and validate chemical protocols to synthesise peptide-compound hybrid molecules (HMs). As a proof of concept, reporter fluorophores have been added to two candidate peptides:

Our objective: efficient synthesis of a family of HMs with the ability to target the central nervous system and more specifically oligodendroglial lineage cells.
Results: we have synthesised two peptides conjugated to fluorophores.
Next steps: We are looking into the extended possibility of using quantum dots and nanoparticles to further assess signal stability and pharmacokinetics of the HMs, as well as introducing candidate therapeutic molecules as cargo for the HMs.

In cell and in vivo study of pharmacokinetics of HMs. We have treated cells and mice with these HMs in order to assess anatomical and cellular distribution:

Our objective in vivo: in this first approach, to assess HMs in terms of their pharmacokinetic properties in order to find the most efficient ones crossing the blood-brain barrier and specifically target oligondendroglial lineage cells.
Results in vivo: we have observed presence of our molecules in brain in histological samples, as well as in other inner organs of the mouse. This could be interesting as a possible patent for HMs delivery to these organs.
Next steps: further assess pharmacokinetics and chemical stability of the HMs in vivo over time.
Our objective in cell: assess the intake (endocytosis) and co-localization of our reporter fluorophores in different type of brain cells.
Results: we have obtained mixed results in different approaches: we have performed HMs treatment in cell in mixed brain cell cultures and in organotypic slices.
Next steps: titration of HMs dosage for these experiments. Possibly assessing cell intake of the HMs through flow-cytometry.

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