Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quetiapine (Que), a commonly used atypical antipsychotic drug (APD), can prevent myelin from breakdown without immune attack. Multiple sclerosis (MS), an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells). In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. Que treatment was initiated on the onset of MOG(35-55) peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4(+)/CD8(+) populations and the proliferation of effector T cells (CD4(+)CD25(-)) in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4(+)/CD8(+) T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4(+)/CD8(+) T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG(35-55) or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4(+)CD25(-)) isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.
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PMID:Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation. 2291 31

Multiple sclerosis (MS) is a central nervous system disorder that is associated with progressive oligodendrocyte and neuronal loss, axonal degeneration, and demyelination. Several medications that mitigate immune abnormalities reduce both the frequency of relapses and inflammation on magnetic resonance imaging, leading to improved outcomes for people with the relapsing-remitting form of MS. However, there are no treatments for the progressive forms of MS where neurons and axons continue to degenerate; here, neuroprotective therapies, or medications that rebuild myelin to confer axonal well-being, may be useful. Quetiapine fumarate is an atypical antipsychotic with reported remyelinating and neuroprotective properties in inflammatory and noninflammatory models of demyelination, including experimental autoimmune encephalomyelitis, and both cuprizone- and global cerebral ischemia-induced demyelination. Preclinical studies suggest that quetiapine may exert these effects by stimulating proliferation and maturation of oligodendrocytes, releasing neurotrophic factors, increasing antioxidant defences, scavenging for free radicals, and inhibiting activated microglia, astrocytes, and T lymphocytes. Additionally, quetiapine may be beneficial for psychiatric and nonpsychiatric symptoms of MS including depression, anxiety, insomnia, and possibly even pain. These data indicate that clinical trials are justified to determine the safety, tolerability, and efficacy of quetiapine fumarate in MS.
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PMID:Quetiapine fumarate for the treatment of multiple sclerosis: focus on myelin repair. 2387 Jun 12