Mechanisms of treatment of Rett syndrome with ghrelin administration

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15692
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kurume University
• Principal Investigator: Yuge Kotaro 久留米大学, 医学部, 助教 (20624472)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: レット症候群 / グレリン / 治療メカニズム

Outline of Final Research Achievements

Rett syndrome (RTT) is a neurodevelopmental disorder that develops in infancy and is characterised by severe intellectual disability, autism, epilepsy, sleep disturbance and dystonia, and is mainly caused by MeCP2 mutations. The applicant has focused on the diverse physiological activities of ghrelin, a gastric and intestinal hormone, and has conducted research on RTT treatment with ghrelin. As a result of this research, the therapeutic mechanism was analysed using an RTT model (MeCP2-deficient) mouse, as it was found that the treatment improved dystonia, sleep and constipation. The study found that improvement of dopamine and noradrenaline reactivity as well as improvement of the autonomic nervous system were suggested as treatment mechanisms.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

本研究では、グレリン治療のメカニズムとしてRTTモデルマウスにてドパミン・ノルアドレナリン反応性の改善、また自律神経症状の改善が示唆されることを見出した。これらの成果は臨床におけるRTTに対するグレリン治療法開発の一助となる可能性がある。また本研究の評価方法や結果はRTTの病態解明へつながり、さらに自閉症や知的障害などの神経発達症、また付随することの多い睡眠障害やてんかんなどの病態解明にもつながる可能性がある。