Elucidation of the pathogenesis of creatine metabolism dysregulation in spinal and bulbar muscular atrophy (SBMA) and clinical trial of oral creatine for patients with SBMA

2014 Fiscal Year Final Research Report

• Project/Area Number: 26670440
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: KASTUNO Masahisa 名古屋大学, 医学(系)研究科(研究院), 准教授 (50402566)
• Co-Investigator(Kenkyū-buntansha): SOBUE Gen 名古屋大学, 医学系研究科, 教授 (20148315)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Keywords: 球脊髄性筋萎縮症 / 神経変性疾患 / 運動ニューロン / 骨格筋 / クレアチン

Outline of Final Research Achievements

Serum creatinine (Cr) levels decrease with disease progression of spinal and bulbar muscular atrophy (SBMA). To elucidate the pathogenesis of creatine-Cr metabolism dysregulation in SBMA, we included subjects with SBMA (n = 52) to assess motor function using functional parameters and measure muscle mass with dual-energy X-ray absorptiometry (DXA). We also examined the intra-muscular creatine concentration and analyzed the expression levels of creatine transporter in skeletal muscle using immunoblotting. Serum Cr levels correlated well with the functional parameters such as ALSFRS-R in SBMA. Both serum Cr and muscular creatine levels were lower in SBMA than in ALS, even though these groups had similar ALST. Furthermore, the expression levels of muscular creatine transporter were decreased in SBMA compared with ALS, providing a molecular basis for the decreased intra-muscular creatine in SBMA.

Free Research Field

神経内科学