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イシガキ ケイコ
ISHIGAKI Keiko
石垣 景子 所属 医学部 医学科（東京女子医科大学病院） 職種 准教授 |
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| 論文種別 | 総説 |
| 言語種別 | 英語 |
| 査読の有無 | 査読なし |
| 表題 | Fukuyama congenital muscular dystrophy: Clinical features and therapeutic advances |
| 掲載誌名 | 正式名：Brain & Development 略 称：Brain Dev ISSNコード：18727131 |
| 掲載区分 | 国外 |
| 出版社 | Elsevier |
| 巻・号・頁 | 47(5),pp.104437 |
| 著者・共著者 | ISHIGAKI Keiko, TANIGUCHI-IKEDA Mariko |
| 発行年月 | 2025/09/05 |
| 概要 | Abstract
Fukuyama congenital muscular dystrophy (FCMD, a severe form of muscular dystrophy characterized by brain structural anomalies and ocular complications due to neuronal migration disorders, is notably limited mainly to Japan. Ninety percent of patients are unable to walk throughout their lives and die before the age of 20 due to respiratory failure and cardiomyopathy. At present, there is no cure. The founder variant, a 3-kb insertion in FKTN, is an SVA (SINE-VNTR-Alu) retrotransposon, and FCMD is a splicing disorder attributable the exon trapping function of this retrotransposon. A splicing modulation therapy targeting exon-trapping based on using antisense nucleic acids to block abnormal splicing is under development, and clinical trials have begun. Additionally, it was clarified that the gene product of FKTN is a glycosyltransferase that transfers ribitol-5-phosphate from cytidine diphosphate ribitol, a precursor for the synthesis of the O-mannosyl glycans of α-dystroglycan, a cell membrane component. This finding raises hopes for a prodrug therapy. Though patient numbers were small, previous clinical studies suggested that steroids are effective in FCMD. Thus, phase II clinical trials are underway with the aim of obtaining insurance approval. This review provides an overview of the clinical course and current status of treatments being developed for FCMD. |
| DOI | 10.1016/j.braindev.2025.104437 |
| PMID | 40914050 |