Heparan Sulphate mimetics as a therapeutic for central nervous system repair

Sherrard Smith, R., Lindsay, S.L. , Goodyear, C. , Turnbull, J. and Barnett, S.C. (2021) Heparan Sulphate mimetics as a therapeutic for central nervous system repair. XV European Meeting on Glial Cells in Health and Disease, 5-9 July 2021. E513-E514. (doi: 10.1002/glia.24036)

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Demyelination and axonal pathology in the central nervous system (CNS) is associated with numerous neurological disorders such as spinal cord injury (SCI) and multiple sclerosis (MS). Any repair strategies for CNS damage must have a multifactorial approach including promotion of axonal outgrowth, and remyelination. One such candidate is heparin sulphate mimetics which are glycomolecules of repeating disaccharide units synthesised from heparin (mHeps) to express varying levels of sulphation and lack coagulation activity. They share structural similarities to cellular heparan suphates (HS) which modulate a huge range of cellular function. They are thought to regulate a variety of cell signalling by both sequestering ligands and acting as a cofactor in the formation of ligand-receptor complexes. Using these mimetics, we have demonstrated that low sulphated mimetics (LS-mHeps) enhance neurite outgrowth and myelination in vitro by sequestering molecules that inhibit myelination. Thus, LS-mHeps have the capacity to represent novel candidates as therapeutics for CNS damage. Here, we test our lead compound, in an ex vivo and in vivo model namely experimental autoimmune encephalomyelitis (EAE) and mouse cerebellum slice cultures. LS-mHep7 treated EAE animals recovered faster and had reduced numbers of inflammatory cells within spinal cord lesions. Interestingly, LS-mHep7 promoted a more rapid restoration of pre-disease animal weight and promoted appetite directly in non-diseased animals. This suggests LS-mHep7 has beneficial effects on both animal welfare and appetite. Ex vivo data shows similar promotion of myelination supporting the future clinical translation of these next generation heparin mimetics as a novel treatment for CNS diseases.

Item Type:Conference or Workshop Item
Glasgow Author(s) Enlighten ID:Sherrard Smith, rebecca and Barnett, Professor Susan and Lindsay, Dr Susan and Goodyear, Professor Carl
Authors: Sherrard Smith, R., Lindsay, S.L., Goodyear, C., Turnbull, J., and Barnett, S.C.
Subjects:Q Science > Q Science (General)
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Glia
Published Online:26 June 2021

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
308223SPRINT-MND/MS Studentship Award -Rebecca SmithSusan BarnettUniversity of Edinburgh (HEI-EDIN)SPRINT19/SMITH-3752534III - Immunology
309989Heparin mimetics: Novel non-anticoagulant compounds to promote CNS repairSusan BarnettMedical Research Council (MRC)MR/V00381X/1III - Immunology