| アブストラクト | BACKGROUND: Alterations in bile acid metabolism have been observed in individuals with multiple sclerosis (MS), yet the therapeutic implications of bile acid supplementation remain uncertain. METHODS: We conducted a two-stage study integrating pharmacovigilance analysis with preclinical validation to evaluate bile acid derivatives as candidate therapies for MS. A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4/2003-Q2/2025) was performed to identify inverse associations between MS and bile acid preparations. The effects of ursodeoxycholic acid (UDCA) and obeticholic acid (6-ECDCA) were evaluated in a therapeutic experimental autoimmune encephalomyelitis (EAE) model, with treatment initiated after disease onset. RESULTS: Among 13,734,539 FAERS reports, 75,659 involved MS. Inverse associations were identified for UDCA (odds ratio [OR]: 0.197, 95% confidence interval [CI]: 0.117-0.333) and 6-ECDCA (OR: 0.128, 95% CI: 0.041-0.396). In the EAE model, UDCA was associated with lower clinical scores at the peak (day 18) and late phases (days 26-28), whereas 6-ECDCA showed only a non-significant trend toward improvement at day 28. CONCLUSION: This two-stage investigation highlights the potential utility of pharmacovigilance-guided approaches for identifying therapeutic candidates. Bile acid derivatives, particularly UDCA, are biologically plausible candidates meriting further investigation in the context of MS. |
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| 投稿者 | Asada, Mizuho; Aizawa, Fuka; Mikami, Takahisa; Goda, Mitsuhiro; Sonoda, Yuhei; Niimura, Takahiro; Zamami, Yoshito; Chuma, Masayuki; Uesawa, Yoshihiro; Ishizawa, Keisuke |
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| 組織名 | Department of Medical Molecular Informatics, Meiji Pharmaceutical University,;2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan. Electronic address:;mizuho@my-pharm.ac.jp.;Department of Pharmacy, Tokushima University Hospital, 2-50-1 Kuramoto-cho,;Tokushima-shi, Tokushima 770-8503, Japan; Department of Clinical Pharmacology and;Therapeutics, Tokushima University Graduate School of Biomedical Sciences,;3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8504, Japan. Electronic;address: f_aizawa@tokushima-u.ac.jp.;Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston,;MA 02114, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.;Electronic address: tmikami@mgh.harvard.edu.;Department of Clinical Pharmacology and Therapeutics, Graduate School of;Biomedical and Health Sciences, Hiroshima University, Japan. Electronic address:;mitsuhirogoda@hiroshima-u.ac.jp.;address: sonoda.yuuhei@tokushima-u.ac.jp.;Department of Clinical Pharmacology and Therapeutics, Tokushima University;Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima-shi,;Tokushima 770-8504, Japan; Clinical Research Center for Developmental;Therapeutics, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima-shi,;Tokushima 770-8503, Japan. Electronic address: niimura@tokushima-u.ac.jp.;Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku,;Okayama 700-8558, Japan; Department of Clinical Pharmacology and Pharmacy,;Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.;Electronic address: zamami-y@okayama-u.ac.jp.;Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University;and University Hospital, Midorigaoka Higashi 2-1-1-1, Asahikawa-shi, Hokkaido;078-8510, Japan. Electronic address: chuma-masayuki@asahikawa-med.ac.jp.;uesawa@my-pharm.ac.jp.;3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8504, Japan; Department of;Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health;Sciences, Hiroshima University, Japan. Electronic address:;ishizawa@tokushima-u.ac.jp. |
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