Bryostatin-1 alleviates experimental multiple sclerosis.

Autor:	Kornberg MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287., Smith MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287., Shirazi HA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287., Calabresi PA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Snyder SH; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287; ssnyder@jhmi.edu pmkim@jhmi.edu.; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Kim PM; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287; ssnyder@jhmi.edu pmkim@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Feb 27; Vol. 115 (9), pp. 2186-2191. Date of Electronic Publication: 2018 Feb 12.
DOI:	10.1073/pnas.1719902115
Abstrakt:	Multiple sclerosis (MS) is an inflammatory disorder targeting the central nervous system (CNS). The relapsing-remitting phase of MS is largely driven by peripheral activation of autoreactive T-helper (Th) 1 and Th17 lymphocytes. In contrast, compartmentalized inflammation within the CNS, including diffuse activation of innate myeloid cells, characterizes the progressive phase of MS, the most debilitating phase that currently lacks satisfactory treatments. Recently, bryostatin-1 (bryo-1), a naturally occurring, CNS-permeable compound with a favorable safety profile in humans, has been shown to act on antigen-presenting cells to promote differentiation of lymphocytes into Th2 cells, an action that might benefit Th1-driven inflammatory conditions such as MS. In the present study, we show that bryo-1 provides marked benefit in mice with experimental autoimmune encephalomyelitis (EAE), an experimental MS animal model. Preventive treatment with bryo-1 abolishes the onset of neurologic deficits in EAE. More strikingly, bryo-1 reverses neurologic deficits after EAE onset, even when treatment is initiated at a late stage of disease when peak adaptive immunity has subsided. Treatment with bryo-1 in vitro promotes an anti-inflammatory phenotype in antigen-presenting dendritic cells, macrophages, and to a lesser extent, lymphocytes. These findings suggest the potential for bryo-1 as a therapeutic agent in MS, particularly given its established clinical safety. Furthermore, the benefit of bryo-1, even in late treatment of EAE, combined with its targeting of innate myeloid cells suggests therapeutic potential in progressive forms of MS. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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