Kennedy's disease: clinical significance of tandem repeats in the androgen receptor.

Abstract

Kennedy's disease (KD) or spinobulbar muscular atrophy is a hereditary X-linked, progressive neurodegenerative condition caused by an expansion of the CAG triplet repeat in the first exon of the androgen receptor gene. The phenotype in its full form is only expressed in males and presents as weakness and wasting of the upper and lower limbs and bulbar muscles associated with absent reflexes. Sensory disturbances are present. Various endocrine abnormalities including decreased fertility and gynecomastia are common and amongst the first features of KD. Animal models of KD have demonstrated improvement on withdrawal of testosterone, indicating that this agonist of the androgen receptor is required for the toxic effect. Potential therapies based on testosterone withdrawal in humans have shown some promise, but efficacy remains to be proven. Potential clinical factors, pathogenesis and future approaches to therapy are reviewed in this chapter.

• Authors: Jeffrey D Zajac, Mark Ng Tang Fui
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 769 Pg. 153-68 ( 2012) ISSN: 0065-2598 [Print] United States
• PMID: 23560310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• AR protein, human
• Drugs, Investigational
• Peptides
• Receptors, Androgen
• polyglutamine
• Testosterone
• Aromatase

Topics

• 46, XX Disorders of Sex Development (physiopathology)
• Aromatase (deficiency)
• Bulbo-Spinal Atrophy, X-Linked (drug therapy, genetics, metabolism, physiopathology)
• Drugs, Investigational (pharmacology, therapeutic use)
• Exons
• Gynecomastia (physiopathology)
• Humans
• Infertility, Male (physiopathology)
• Male
• Metabolism, Inborn Errors (physiopathology)
• Peptides (genetics)
• Receptors, Androgen (genetics, metabolism)
• Sex Factors
• Testosterone (antagonists & inhibitors, metabolism)
• Trinucleotide Repeat Expansion