APC-mediated tolerance induction for therapy of multiple sclerosis

Abstract

The invention relates to transgene expression constructs—particularly self inactivating lentiviral vectors—comprising a dendritic cell specific promoter controlling the expression of autoantigen proteins, namely myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein, for use in the therapy of multiple sclerosis.

Description

Background technique [0001] The causes of multiple sclerosis (MS or disseminated encephalomyelitis) are not well understood and the pathogenic processes leading to the disease are not fully understood. Current knowledge supports the pathogenesis of T cell-mediated autoimmunity targeting myelin components or myelin-producing cells. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are characterized by the activation and accumulation of antigen-presenting cells (APCs) and autoreactive lymphocytes within the central nervous system (CNS). Some of the myelin proteins known to be recognized by autoreactive T cells include myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). [0002] Myelin basic protein (MBP) is a major component of the myelin sheath of oligodendrocytes and Schwann cells. The genetic data of its human orthologue is publicly available at the US National Center for Biotechnology Information (NCB...

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Problems solved by technology

These investigators used a constitutive promoter that mediates MOG expression in different hematopoietic cells, which can cause unwanted side effects

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