Enhanced myelination in autoimmunity and in normal development induced by glatiramer acetate.

M ultiple sclerosis (MS) is a complex multifaceted disease in which inflammatory autoimmune attack in the central nervous system (CNS) leads to the destruction of the myelin sheath and the formation of demyelinated lesions in the white matter [1]. Diffused molecular and cellular changes in normal-appearing white matter and cortical demyelination have also been recognized as a component of MS pathology. This widespread demyelination results in impaired nerve conductivity and neuroaxonal damage. Thus, the essential challenge for MS therapy is not only to ameliorate the inflammatory aspect of the disease, but to promote neuroprotective repair mechanisms beyond their limited spontaneous occurrence, in particular remyelination. Glatiramer acetate (GA, Copaxone®, Israel) is an amino acid copolymer, an approved drug widely used as a first-line treatment for MS [2]. Cumulative evidences indicate that GA affects various levels of the innate and the adaptive immune response, inducing deviation from pro-inflammatory to anti-inflammatory pathways [3]. This includes competition for the binding of antigen-presenting cells, driving dendritic cells, monocytes, and B cells towards anti-inflammatory responses, induction of Th2/3 and T-regulatory cells, and down-regulation of both Th1 and Th17 cells. The immune cells induced by GA reach into the CNS and secrete in situ anti-inflammatory cytokines, thus alleviating the pathological inflammatory processes [4]. In addition to its immunomodulatory activity, GA treatment induces elevation in the CNS levels of several neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), suggesting neuroprotective repair consequences [5]. To examine whether GA can indeed affect the repair and remyelination we applied two systems: the animal model of MS, experimental autoimmune encephalomyelitis (EAE), and postnatal myelination in the developing CNS of newborn mice. REMYElInATIon In EAE