Towards a Minimally Invasive Regenerative Gene Therapy for Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) characterized by focal demyelinating lesions throughout CNS. Current treatments for MS primarily target the immune system and are efficacious during the early phase of MS. Current MS treatments are largely ineffective at alleviating clinical symptoms or slowing disease progression during the progressive stages of MS, nor do they promote the repair of pre-existing damage. Therefore, there is an unmet medical need for strategies that directly target demyelinated regions of the CNS with the goal to repair existing injury in MS. The overall goal of this thesis is to develop a minimally invasive regenerative gene therapy for MS. The specific aims of this thesis are: 1. To investigate whether a systemic gene therapy can be deployed in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS with high specificity to the CNS, 2. To examine whether specific neural cell types associated with EAE-lesions and with a putative role in regeneration in MS (e.g., astrocytes, oligodendrocytes, and oligodendrocyte precursor cells (OPCs)) can be targeted by a minimally invasive gene therapy, and 3. To establish whether minimally invasive gene therapy can be used in the EAE mouse model to promote remyelination and recovery of function by interfering with chemorepulsive signalling. By implementing a minimally invasive gene therapy, we aim to pioneer new regenerative therapeutic avenues to restore myelination and functional recovery in MS.