Validation of Recombinant Heparan Sulphate Reagents for CNS Repair

Lindsay, Susan LL, Smith, Rebecca Sherrard, Yates, Edwin AA ORCID: 0000-0001-9365-5433, Cartwright, Colin, Thacker, Bryan EE, Turnbull, Jeremy EE, Glass, Charles AA and Barnett, Susan CC (2023) Validation of Recombinant Heparan Sulphate Reagents for CNS Repair. BIOLOGY-BASEL, 12 (3). 407-.

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Official URL: http://dx.doi.org/10.3390/biology12030407

Abstract

Therapies that target the multicellular pathology of central nervous system (CNS) disease/injury are urgently required. Modified non-anticoagulant heparins mimic the heparan sulphate (HS) glycan family and have been proposed as therapeutics for CNS repair since they are effective regulators of numerous cellular processes. Our <i>in vitro</i> studies have demonstrated that low-sulphated modified heparan sulphate mimetics (LS-mHeps) drive CNS repair. However, LS-mHeps are derived from pharmaceutical heparin purified from pig intestines, in a supply chain at risk of shortages and contamination. Alternatively, cellular synthesis of heparin and HS can be achieved using mammalian cell multiplex genome engineering, providing an alternative source of recombinant HS mimetics (rHS). TEGA Therapeutics (San Diego) have manufactured rHS reagents with varying degrees of sulphation and we have validated their ability to promote repair <i>in vitro</i> using models that mimic CNS injury, making comparisons to LS-mHep7, a previous lead compound. We have shown that like LS-mHep7, low-sulphated rHS compounds promote remyelination and reduce features of astrocytosis, and in contrast, highly sulphated rHS drive neurite outgrowth. Cellular production of heparin mimetics may, therefore, offer potential clinical benefits for CNS repair.

Item Type:	Article
Uncontrolled Keywords:	heparan sulphate, recombinant heparin mimetics, CNS repair, remyelination, neurite outgrowth
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	18 Apr 2023 08:40
Last Modified:	19 Apr 2023 10:56
DOI:	10.3390/biology12030407
Open Access URL:	https://doi.org/10.3390/biology12030407
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3169639