Faculty Profiles - HASHIZUME Atsushi

Papers - HASHIZUME Atsushi

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リュープロレリン酢酸塩の球脊髄性筋萎縮症患者に対する第3相長期継続投与試験(JASMITT-07OP試験) Reviewed

鈴木啓介, 勝野雅央, 坂野晴彦, 須賀徳明, 橋詰淳, 矢部一郎, 青木正志, 中野今治, 金井数明, 水澤英洋, 山本知孝, 長谷川一子, 西澤正豊, 宮嶋裕明, 苅田典生, 中島健二, 辻野彰, 内野誠, 田中章景, 祖父江元

臨床神経学 Vol. 52 ( 12 ) page： 1484 - 1484 2012.12

嚥下造影3回法の信頼性・妥当性の検討 SBMAを例に Reviewed

坂野晴彦, 勝野雅央, 鈴木啓介, 須賀徳明, 橋詰淳, 眞野智生, 田中誠也, 山本正彦, 祖父江元

臨床神経学 Vol. 52 ( 12 ) page： 1516 - 1516 2012.12

球脊髄性筋萎縮症における発声障害の定量的検討 Reviewed

田中誠也, 坂野晴彦, 勝野雅央, 鈴木啓介, 眞野智生, 須賀徳明, 橋詰淳, 山本正彦, 祖父江元

臨床神経学 Vol. 52 ( 12 ) page： 1514 - 1514 2012.12

球脊髄性筋萎縮症患者におけるリュープロレリン酢酸塩長期使用成績定量的筋力解析を用いた検討 Reviewed

須賀徳明, 勝野雅久, 坂野晴彦, 鈴木啓介, 橋詰淳, 眞野智生, 祖父江元

臨床神経学 Vol. 52 ( 12 ) page： 1604 - 1604 2012.12

球脊髄性筋萎縮症の自然歴の検討(3年間の前向き研究) Reviewed

橋詰淳, 勝野雅央, 坂野晴彦, 鈴木啓介, 須賀徳明, 眞野智生, 田中章景, 祖父江元

臨床神経学 Vol. 52 ( 12 ) page： 1514 - 1514 2012.12

球脊髄性筋萎縮症に対する疾患特異的機能評価スケール(SBMAFRS)の開発と信頼性・妥当性評価 Reviewed

真野智生, 勝野雅央, 坂野晴彦, 鈴木啓介, 須賀徳明, 橋詰淳, 田中章景, 祖父江元

臨床神経学 Vol. 52 ( 12 ) page： 1604 - 1604 2012.12

Cross-sectional and longitudinal analysis of an oxidative stress biomarker for spinal and bulbar muscular atrophy. Reviewed International journal

Tomoo Mano, Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Noriaki Suga, Atsushi Hashizume, Fumiaki Tanaka, Gen Sobue

Muscle & nerve Vol. 46 ( 5 ) page： 692 - 7 2012.11

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. The aim of this study was to verify whether urinary 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, is a biomarker for SBMA. METHODS: We measured the levels of urinary 8-OHdG in 33 genetically confirmed SBMA patients and 32 age-matched controls over a 24-month period at 6-month intervals. RESULTS: Urinary 8-OHdG levels in SBMA patients were significantly elevated compared with those of controls and correlated well with motor function scores. During the follow-up period, urinary 8-OHdG levels increased and correlated with motor function at each time-point. In addition, urinary 8-OHdG levels at baseline were correlated with changes in the 6-minute walk test during 24 months. CONCLUSIONS: Urinary 8-OHdG is a biomarker for SBMA, reflecting the severity and possibly predicting the deterioration of motor function.

DOI： 10.1002/mus.23413

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[109th Scientific Meeting of the Japanese Society of Internal Medicine: symposium: 2. Translational research and evidence-based medicine (EBM) in internal medicine in Japan, translational research; 1) Translational research on neurodegenerative diseases]. Reviewed

Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Atsushi Hashizume, Hiroaki Adachi, Fumiaki Tanaka, Gen Sobue

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine Vol. 101 ( 9 ) page： 2533 - 8 2012.9

Longitudinal changes of outcome measures in spinal and bulbar muscular atrophy. Reviewed International journal Open Access

Atsushi Hashizume, Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Noriaki Suga, Tomoo Mano, Naoki Atsuta, Hiroaki Oe, Hirohisa Watanabe, Fumiaki Tanaka, Gen Sobue

Brain : a journal of neurology Vol. 135 ( Pt 9 ) page： 2838 - 48 2012.9

Language：English Publishing type：Research paper (scientific journal)

Spinal and bulbar muscular atrophy is an adult-onset, hereditary motor neuron disease caused by the expansion of a trinucleotide CAG repeat within the gene encoding the androgen receptor. To date, several agents have been shown to prevent or slow disease progression in animal models of this disease. For the translational research of these agents, it is necessary to perform the detailed analysis of natural history with quantitative outcome measures and to establish sensitive and validated disease-specific endpoints in the clinical trials. To this end, we performed a prospective observation of disease progression over 3 years in 34 genetically confirmed Japanese patients with spinal and bulbar muscular atrophy by using quantitative outcome measures, including functional and blood parameters. The baseline evaluation revealed that CAG repeat length in the androgen receptor gene correlated not only with the age of onset but also with the timing of substantial changes in activity of daily living. Multiple regression analyses indicated that the serum level of creatinine is the most useful blood parameter that reflects the severity of motor dysfunction in spinal and bulbar muscular atrophy. In 3-year prospective analyses, a slow but steady progression was affirmed in most of the outcome measures we examined. In the analyses using random coefficient models that summarize the individual data into a representative line, disease progression was not affected by CAG repeat length or onset age. These models showed large interindividual variation, which was also independent of the differences of CAG repeat size. Analyses using these models also demonstrated that the subtle neurological deficits at an early or preclinical stage were more likely to be detected by objective motor functional tests such as the 6-min walk test and grip power or serum creatinine levels than by functional rating scales, such as the revised amyotrophic lateral sclerosis functional rating scale or modified Norris scale. Categorization of the clinical phenotypes using factor analysis showed that upper limb function is closely related to bulbar function, but not to lower limb function at baseline, whereas the site of onset had no substantial effects on disease progression. These results suggest that patients with spinal and bulbar muscular atrophy show a slow but steady progression of motor dysfunction over time that is independent of CAG repeat length or clinical phenotype, and that objective outcome measures may be used to evaluate disease severity at an early stage of this disease.

DOI： 10.1093/brain/aws170

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知的障害・小脳失調を認め、アキレス腱肥厚から診断しえた脳腱黄色腫症の治療経験 Reviewed

桝田道人, 橋詰淳, 伊藤瑞規, 熱田直樹, 渡辺宏久, 祖父江元

神経治療学 Vol. 29 ( 5 ) page： 659 - 659 2012.9

Difference in chronological changes of outcome measures between untreated and placebo-treated patients of spinal and bulbar muscular atrophy. Reviewed International journal

Atsushi Hashizume, Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Noriaki Suga, Fumiaki Tanaka, Gen Sobue

Journal of neurology Vol. 259 ( 4 ) page： 712 - 9 2012.4

Language：English Publishing type：Research paper (scientific journal)

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked motor neuron disease characterized by muscle atrophy, weakness, and bulbar involvement. The aim of this study was to analyze the differential change of various outcome measures by comparing the progression of motor impairment in the two independent groups: placebo-treated group (PTG) and natural history group (NHG). For the PTG, we analyzed 99 patients who participated in a previous double-blind phase III clinical trial and received placebo. For the NHG, a total of 34 patients were followed with no specific treatment. The characteristics of both groups did not differ at baseline except for disease duration. Although the 6 min walk distance (6MWD) showed almost the same progression in both groups (-14.7 ± 7.3 m in NHG, -14.0 ± 4.7 m in PTG; NS), there was a significant difference of progression in the ALSFRS-R between the NHG and PTG (-1.18 ± 0.38, -0.14 ± 0.24; p = 0.03). A similar tendency was also seen in the subgroup analysis of the patients whose disease durations were less than 10 years. Although the relationship between the ALSFRS-R and 6MWD at week 48 was similar to that at baseline in the NHG, the slope of the regression at week 48 was significantly milder than at baseline in the PTG (p = 0.04). In conclusion, these two groups demonstrated a large difference in the chronological analysis of a motor function score, but showed similar changes in objective measures of walking capacity. These findings should be thoroughly considered when designing clinical trials for slowly progressive neurodegenerative diseases such as SBMA.

DOI： 10.1007/s00415-011-6251-2

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水頭症術後に眼球運動障害とパーキンソニズムを呈し、中脳水道開窓術が有効であった中脳水道狭窄症の2例 Reviewed

桝田道人, 橋詰淳, 伊藤瑞規, 熱田直樹, 渡辺宏久, 祖父江元, 種村衣里子, 永谷哲也

臨床神経学 Vol. 52 ( 4 ) page： 273 - 273 2012.4

[Anti-androgen therapy for spinal and bulbar muscular atrophy (SBMA)]. Reviewed Open Access

Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Atsushi Hashizume, Hiroaki Adachi, Fumiaki Tanaka, Gen Sobue

Rinsho shinkeigaku = Clinical neurology Vol. 52 ( 11 ) page： 1207 - 9 2012

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Societas Neurologica Japonica

Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is an adult-onset lower motor neuron disease caused by the expansion of a trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of the androgen receptor (AR) gene. The testosterone-dependent nuclear accumulation of polyglutamine-expanded AR protein is central to the pathogenesis. This hypothesis is supported by pre-clinical studies showing that testosterone deprivation ameliorates motor neuron degeneration in animal modes of SBMA. In a randomized placebo-controlled multi-centric clinical trial, leuprorelin, which suppresses secretion of testosterone, showed no definite effect on motor functions, although there was the improvement of swallowing function in a subgroup of patients whose disease duration was less than 10 years. Elucidation of the entire disease mechanism, early initiation of therapeutic intervention, and sensitive outcome measures to evaluate drug effect appear to be the key to a successful translational research on SBMA.

DOI： 10.5692/clinicalneurol.52.1207

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CiNii Research

1) Translational Research on Neurodegenerative Diseases

Katsuno Masahisa, Banno Haruhiko, Suzuki Keisuke, Hashizume Atsushi, Adachi Hiroaki, Tanaka Fumiaki, Sobue Gen

Nihon Naika Gakkai Zasshi Vol. 101 ( Suppl ) page： 113a - 113a 2012