Title:Immunotherapy Strategies for Spinal Cord Injury
Volume: 16
Issue: 6
Author(s): Yong-Tang Wang, Xiu-Min Lu, Kai-Ting Chen, Ya-Hai Shu and Chun-Hong Qiu
Affiliation:
Keywords:
Immunotherapy, inflammation, myelin-associated inhibitors (MAIs), Nogo, myelin-associated glycoprotein
(MAG), oligodendrocyte-myelin glycoprotein (OMgp), Nogo-66 receptor (NgR), myelin basic protein (MBP), myelin oligodendrocyte
glycoprotein (MOG), axon regeneration, spinal cord injury, experimental autoimmune encephalomyelitis (EAE).
Abstract: Regeneration in the central nervous system (CNS) of adult mammalian after
traumatic injury is limited, which often causes permanent functional motor and sensory
loss. After spinal cord injury (SCI), the lack of regeneration is mainly attributed to the
presence of a hostile microenvironment, glial scarring, and cavitation. Besides, inflammation
has also been proved to play a crucial role in secondary degeneration following
SCI. The more prominent treatment strategies in experimental models focus mainly on drugs and cell therapies, however,
only a few strategies applied in clinical studies and therapies still have only limited effects on the repair of SCI. Recently,
the interests in immunotherapy strategies for CNS are increasing in number and breadth. Immunotherapy strategies have
made good progresses in treating many CNS degenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease
(PD), stroke, and multiple sclerosis (MS). However, the strategies begin to be considered to the treatment of SCI and
other neurological disorders in recent years. Besides anti-inflamatory therapy, immunization with protein vaccines and
DNA vaccines has emerged as a novel therapy strategy because of the simplicity of preparation and application. An inflammatory
response followed by spinal cord injury, and is controled by specific signaling molecules, such as some cytokines
playing a crucial role. As a result, appropriate immunoregulation, the expression of pro-inflammatory cytokines and
anti-inflammatory cytokines may be an effective therapy strategy for earlier injury of spinal cord. In addition, myelinassociated
inhibitors (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-
myelin glycoprotein (OMgp) are known to prevent axonal regeneration through their co-receptors, and to
trigger demyelinating autoimmunity through T cell-mediated harmful autoimmune response. The antagonism of the MAIs
through vaccinating with protein or DNA vaccines targeting Nogo, MAG, OMgp, and their co-receptors, may be an effective
strategy for the treatment of SCI. However, immunotherapy such as anti-inflammtory therapy or vaccine targeting
MAIs or their receptors, accompanied with the potential in risking autoimmune diseases. As a result, in order to optimize
the anti-inflammtory therapy and design of protein or DNA vaccines for their use in the future clinical application, we
need to further understand the possible mechanisms of neuroprotective immunity. This review presents recent advances in
the development of immunotherapy strategies for the treatment of axonal degeneration and demyelination, and improvement
of motor function after SCI.
