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Therapeutic approaches to spinal and bulbar muscular atrophy.

Ranganathan, Srikanth LU and Fischbeck, Kenneth H (2010) In Trends in Pharmacological Sciences Okt. p.523-527
Abstract
Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a different phenotype and the mutant protein is toxic in mouse models. In these models, the toxicity is ligand-dependent and is associated with protein aggregation, as well as altered transcriptional regulation, axonal transport and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction, heat shock protein 90 (HSP90) inhibition and insulin-like growth factor (IGF)-1... (More)
Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a different phenotype and the mutant protein is toxic in mouse models. In these models, the toxicity is ligand-dependent and is associated with protein aggregation, as well as altered transcriptional regulation, axonal transport and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction, heat shock protein 90 (HSP90) inhibition and insulin-like growth factor (IGF)-1 overexpression. Clinical trials of androgen-reducing agents have had mixed results, with indications of efficacy but no proof of clinically meaningful benefit to date. These clinical studies have established outcome measures for future trials of other agents that have been beneficial in animal studies. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Trends in Pharmacological Sciences
volume
Okt
pages
523 - 527
publisher
Elsevier
external identifiers
  • WOS:000284499900004
  • PMID:20863580
  • Scopus:77958150581
ISSN
0165-6147
DOI
10.1016/j.tips.2010.08.005
language
English
LU publication?
yes
id
4c30a809-05ea-424f-aa4d-b9d29fbe2f2c (old id 1687940)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20863580?dopt=Abstract
date added to LUP
2010-10-06 08:26:04
date last changed
2016-10-13 04:35:42
@misc{4c30a809-05ea-424f-aa4d-b9d29fbe2f2c,
  abstract     = {Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a different phenotype and the mutant protein is toxic in mouse models. In these models, the toxicity is ligand-dependent and is associated with protein aggregation, as well as altered transcriptional regulation, axonal transport and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction, heat shock protein 90 (HSP90) inhibition and insulin-like growth factor (IGF)-1 overexpression. Clinical trials of androgen-reducing agents have had mixed results, with indications of efficacy but no proof of clinically meaningful benefit to date. These clinical studies have established outcome measures for future trials of other agents that have been beneficial in animal studies.},
  author       = {Ranganathan, Srikanth and Fischbeck, Kenneth H},
  issn         = {0165-6147},
  language     = {eng},
  pages        = {523--527},
  publisher    = {ARRAY(0x94c6920)},
  series       = {Trends in Pharmacological Sciences},
  title        = {Therapeutic approaches to spinal and bulbar muscular atrophy.},
  url          = {http://dx.doi.org/10.1016/j.tips.2010.08.005},
  volume       = {Okt},
  year         = {2010},
}