Dissolived Disulfiram resucues mice model of Menkes disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Tohoku University
• Principal Investigator: Mitsutoshi Munakata 東北大学, 医学系研究科, 非常勤講師 (30312573)
• Co-Investigator(Kenkyū-buntansha): 佐藤 恭弘 帝京大学, 医学部, 助教 (00750241) ; 鈴木 亮 帝京大学, 薬学部, 教授 (90384784) ; 児玉 浩子 帝京平成大学, 未登録, 特任教授 (00093386)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Menkes disease / Macular mouse / Copper

Outline of Final Research Achievements

Menkes disease is a severe X-chromosome-linked disorder caused by mutations in a copper transporter, ATP7A. Disulfiram (DSF), a drug used for alcohol addiction treatment, forms a complex with free copper in diet and in body tissue and delivers copper to the brain. In the present study, oral administration of oil-dissolved DSF stably rescued Menkes' disease model mice, accompanied by increased brain weight and copper concentration in the brain. Increased DSF dose, however, reduced brain weight gain. Careful monitoring of DSF concentration might be required for the future clinical use.

Free Research Field

小児科

Academic Significance and Societal Importance of the Research Achievements

Menkes病は銅の吸収不全を来す重篤な遺伝性疾患であり、未治療では致死的である。治療には銅製剤の注射の継続が必要であり、患者、保護者の負担は大きく、効果も限定的である。この疾患におけるDisulfiramの応用は本疾患の経口薬による治療を可能とし、患者の負担を軽減する。また銅の過剰部位から脳へ消化管の負担なく銅を移送するため、治療効果の進展も期待できる。