臨床神経学

第48回日本神経学会総会

<シンポジウム9-4>神経変性疾患の動物モデル
球脊髄性筋萎縮症―病態抑止治療(分子標的治療)への橋渡し―

祖父江 元

名古屋大学大学院医学系研究科 神経内科学〔〒466-8550 名古屋市昭和区鶴舞町65〕

SBMA is a hereditary neurodegenerative disease caused by expansion of a trinucleotide CAG repeat, which encodes the polyglutamine tract, in the first exon of the androgen receptor (AR) gene. The phenotypic difference with gender, which is a specific feature of SBMA, has been recapitulated in a transgenic mouse model of SBMA expressing the full-length human AR containing 97 CAGs under the control of a cytomegalovirus enhancer and a chicken β-actin promoter (AR-97Q). Affected SBMA mice demonstrate small body size, short life span, progressive muscle atrophy and weakness as well as reduced cage activity, all of which are markedly pronounced and accelerated in the male SBMA mice, but either not observed or far less severe in the female SBMA mice. There is increasing evidence that testosterone, the ligand of AR, plays a pivotal role in the neurodegeneration in SBMA. The striking success of androgen deprivation therapy in SBMA mouse models has been translated into phase 2, and then phase 3, clinical trials. Moreover, animal studies have also been revealing key molecules in the pathogenesis of SBMA such as heat shock proteins, transcriptional co-activators, and axon motors, suggesting additional therapeutic targets.

(臨床神経, 47:941−943, 2007)
key words:球脊髄性筋萎縮症, アンドロゲン受容体, トランスジェニックマウス, 病態抑止治療, 酢酸リュープロレリン

(受付日:2007年5月16日)