Pathological elucidation using multi-patients and disease model mice analyses in ADSSL1 myopathy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16589
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Saito Yoshihiko 国立研究開発法人国立精神・神経医療研究センター, メディカルゲノムセンター, 科研費研究員 (80811934)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ADSSL1ミオパチー / 筋病理 / ネマリンミオパチー

Outline of Final Research Achievements

In this study, I found that ADSSL1 myopathy is the most common form of nemaline myopathy in Japan, with a common disease-specific course of muscle pathology, extremely slow and tired legs and slowly progressive muscle weakness in childhood-onset cases, and nemaline bodies and fat droplets in all cases of muscle pathology. In addition, dysphagia, hypertrophic cardiomyopathy, and restricted breathing disorder, which have not been reported before, were found in a high frequency. Furthermore, I have generated ADSSL1 knockout mice and missense knock-in mice to elucidate the pathophysiology and to develop therapeutic strategies.

Free Research Field

筋病理学（遺伝性筋疾患）

Academic Significance and Societal Importance of the Research Achievements

ADSSL1ミオパチーは希少疾患の中でも日本人で現在70名以上診断させている日本で最も頻度の高いネマリンミオパチーであり、本疾患の原因遺伝子はATP de novo合成経路に関わるため代謝性疾患の側面を持ち、治療法開発へ発展させることのできる疾患である。動物モデルを用いて本遺伝子異常による病態や病理に踏み込んでおり、疾患特異的な治療法開発に至ることのできつつあり、他疾患の治療法開発のロールモデルとなり得る可能性がある。