Exploring skeletal muscle pathology in spinal and bulbar muscular atrophy using in silico analysis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15705
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Nagoya University
• Principal Investigator: Iida Madoka 名古屋大学, 医学系研究科, 助教 (40815437)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 球脊髄性筋萎縮症 / 骨格筋病態 / In silico解析 / 治療薬開発

Outline of Final Research Achievements

Spinal and bulbar muscular atrophy (SBMA) is a progressive hereditary neuromuscular disease. We aimed to elucidate the skeletal muscle pathophysiology of SBMA using gene expression analysis information available in the Gene Expression Omnibus (GEO) and the Library of Integrated Network-based Cellular Signatures (LINCS) databases. We identified drugs and their mechanisms of action that induce genetic alterations negatively correlated with the pathophysiology of SBMA. Among them, we selected eight drugs that are expected to ameliorate SBMA pathology. We administered them to a muscle cell model of SBMA and identified drugs that improved SBMA model cell viability and suppressed cell toxicity.
Some of the compounds are existing drugs and have potential for drug repositioning. The mechanism of action of one of the drugs targets the known pathophysiology of SBMA and we plan to confirm its effect in SBMA mouse models in the future.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

球脊髄性筋萎縮症（SBMA）は成人男性のみに発症する進行性の遺伝性神経筋疾患である。約3割の患者は発症後20年で移動に車椅子が必要となり、呼吸筋の筋力低下により呼吸器感染症で死亡することが多い。現在リュープリン酢酸塩がSBMAの唯一の治療薬として日本で承認を受けているが、性ホルモン抑制や骨格筋の同化作用による副作用をみとめ、新規治療薬の開発が望まれている。本研究によりSBMAの病態理解が進み、新たな治療薬開発につながると考えられる。また治療薬開発のプロセスは他の疾患にも応用でき、SBMAのみならず多くの疾患の治療薬開発に結びつくことが期待される。