Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: A pathogenic marker
Article first published online: 15 DEC 2005
Copyright © 2005 American Neurological Association
Annals of Neurology
Volume 59, Issue 3, pages 520–526, March 2006
How to Cite
Banno, H., Adachi, H., Katsuno, M., Suzuki, K., Atsuta, N., Watanabe, H., Tanaka, F., Doyu, M. and Sobue, G. (2006), Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: A pathogenic marker. Ann Neurol., 59: 520–526. doi: 10.1002/ana.20735
- Issue published online: 17 FEB 2006
- Article first published online: 15 DEC 2005
- Manuscript Accepted: 6 OCT 2005
- Manuscript Revised: 4 OCT 2005
- Manuscript Received: 1 SEP 2005
- Ministry of Education, Culture, Sports, Science and Technology, Japan. Grant Number: 17204032
- Ministry of Health, Labor and Welfare, Japan. Grant Number: H-15-Kokoro-020
- Center for Clinical Trials, Japan Medical Association
Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The nuclear accumulation of mutant AR is central to the pathogenesis of SBMA. Androgen deprivation with leuprorelin inhibits mutant AR accumulation, resulting in rescue of neuronal dysfunction in a mouse model of SBMA. This study aimed to investigate whether mutant AR accumulation in the scrotal skin is an appropriate biomarker of SBMA.
Immunohistochemistry of both scrotal skin and the spinal cord was performed on five autopsied SBMA cases. Neurological severity and scrotal skin findings were studied in another 13 patients. Five other patients received subcutaneous injections of leuprorelin and underwent scrotal skin biopsy.
The degree of mutant AR accumulation in scrotal skin epithelial cells tended to be correlated with that in the spinal motor neurons in autopsy specimens, and it was well correlated with CAG repeat length and inversely correlated with the amyotrophic lateral sclerosis functional scale. Leuprorelin treatment inhibited mutant AR protein accumulation in the scrotal skin of SBMA patients.
These observations suggest that scrotal skin biopsy findings are a potent pathogenic marker of SBMA and can be a surrogate end point in therapeutic trials. Ann Neurol 2006