TARGETED DELIVERY OF THE NgR-Fc PROTEIN TO PROMOTE NEUROREPAIR IN A MODEL OF MULTIPLE SCLEROSIS

Abstract

Multiple sclerosis (MS) is an autoimmune-mediated inflammatory demyelinating and degenerative disease
occurring in the central nervous system (CNS). There are no current therapeutics available to treat
patients with progressive MS. Hence, mechanisms that govern CNS neuroprotection and repair need to
be elucidated to provide novel targeted therapeutics to reverse permanent CNS damage. Our laboratory
designed a novel method of delivering the NgR (310) ecto-myc-Fc fusion protein by incorporating the DNA
construct into a lentiviral vector and transducing donor hematopoietic stem cells (HSCs) ex vivo, followed
by their transplantation in recipient mice to target inflammatory demyelinating lesions that ensue during
the MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) mouse model. The aim of this
study was to investigate the potential therapeutic effects of lesion-specific delivery of the NgR (310) ecto-
Fc protein, following the lineage differentiation of the transplanted HSCs, demonstrating neuroprotection
and neurorepair during the course of EAE.