[Molecular-targeted therapy for neurodegenerative diseases].
Neurodegenerative diseases have been construed as incurable disorders. However, therapeutic development for these diseases is now facing a turning point: analyses of cellular and animal models have provided insights into pathogenesis of neurodegenerative diseases, and have indicated rational therapeutic approaches to them. Therefore, how to realize molecular targeted therapy for neurodegenerative diseases is becoming one of the most challenging issues in the clinical neurology. Primarily, pathophysiological understanding of the disease from basic science is the first step. For the successful clinical trials, effective trial design, sufficient economic and social support, and education are indispensable. The development of androgen deprivation therapy for spinal and bulbar muscular atrophy (SBMA) is a representative study in this field. SBMA is a hereditary neurodegenerative disease caused by expansion of a trinucleotide CAG repeat in the first exon of the androgen receptor (AR) gene. 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.
Sobue
Gen
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Department of Neurology, Nagoya University Graduate School of Medicine.
D000726:Androgen Antagonists / Q000627:therapeutic use; D000818:Animals; D055534:Bulbo-Spinal Atrophy, X-Linked / Q000209:etiology / Q000628:therapy; D002986:Clinical Trials as Topic; D005091:Exons / Q000235:genetics; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use; D051379:Mice; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000628:therapy*; D011944:Receptors, Androgen / Q000235:genetics; D013739:Testosterone / Q000502:physiology; D057170:Translational Research, Biomedical; D019680:Trinucleotide Repeat Expansion
D000726:Androgen Antagonists; D011944:Receptors, Androgen; D013739:Testosterone; D016729:Leuprolide