CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis
Abstract Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35...
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Nature Portfolio
2021
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oai:doaj.org-article:5f77b10b118742ed8e9fb83f53cbdc9f2021-12-02T18:30:39ZCKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis10.1038/s41598-021-93232-62045-2322https://doaj.org/article/5f77b10b118742ed8e9fb83f53cbdc9f2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93232-6https://doaj.org/toc/2045-2322Abstract Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.Daekwon BaeJi-Young LeeNina HaJinsol ParkJiyeon BaekDonghyeon SuhHee Seon LimSoo Min KoTaehee KimDa Som JeongWoo-chan SonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) |
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Medicine R Science Q Daekwon Bae Ji-Young Lee Nina Ha Jinsol Park Jiyeon Baek Donghyeon Suh Hee Seon Lim Soo Min Ko Taehee Kim Da Som Jeong Woo-chan Son CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis |
| description |
Abstract Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS. |
| format |
article |
| author |
Daekwon Bae Ji-Young Lee Nina Ha Jinsol Park Jiyeon Baek Donghyeon Suh Hee Seon Lim Soo Min Ko Taehee Kim Da Som Jeong Woo-chan Son |
| author_facet |
Daekwon Bae Ji-Young Lee Nina Ha Jinsol Park Jiyeon Baek Donghyeon Suh Hee Seon Lim Soo Min Ko Taehee Kim Da Som Jeong Woo-chan Son |
| author_sort |
Daekwon Bae |
| title |
CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis |
| title_short |
CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis |
| title_full |
CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis |
| title_fullStr |
CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis |
| title_full_unstemmed |
CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis |
| title_sort |
ckd-506: a novel hdac6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/5f77b10b118742ed8e9fb83f53cbdc9f |
| work_keys_str_mv |
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