PURPOSE OF REVIEW: The aim of this study was to illustrate the current understanding and avenues for developing treatment in spinal and bulbar muscular atrophy (SBMA), an inherited neuromuscular disorder caused by a CAG trinucleotide repeat expansion in the androgen receptor (AR) gene. RECENT FINDINGS: Important advances have been made in characterizing the molecular mechanism of the disease, including the disruption of protein homeostasis, intracellular trafficking and signalling pathways. Biomarkers such as MRI quantification of muscle volume and fat fraction have been used to track disease progression, and will be useful in future clinical studies. Therapies tested and under development have been based on diverse strategies, including targeting mutant AR gene expression, stability and activity, and pathways that mitigate disease toxicity. SUMMARY: We provide an overview of the recent advances in understanding the SBMA disease mechanism and highlight efforts to translate these insights into well tolerated and effective therapy.
PURPOSE OF REVIEW: The aim of this study was to illustrate the current understanding and avenues for developing treatment in spinal and bulbar muscular atrophy (SBMA), an inherited neuromuscular disorder caused by a CAG trinucleotide repeat expansion in the androgen receptor (AR) gene. RECENT FINDINGS: Important advances have been made in characterizing the molecular mechanism of the disease, including the disruption of protein homeostasis, intracellular trafficking and signalling pathways. Biomarkers such as MRI quantification of muscle volume and fat fraction have been used to track disease progression, and will be useful in future clinical studies. Therapies tested and under development have been based on diverse strategies, including targeting mutant AR gene expression, stability and activity, and pathways that mitigate disease toxicity. SUMMARY: We provide an overview of the recent advances in understanding the SBMA disease mechanism and highlight efforts to translate these insights into well tolerated and effective therapy.
Authors: Laura C Bott; Nisha M Badders; Ke-Lian Chen; George G Harmison; Elaine Bautista; Charles C-Y Shih; Masahisa Katsuno; Gen Sobue; J Paul Taylor; Nico P Dantuma; Kenneth H Fischbeck; Carlo Rinaldi Journal: Hum Mol Genet Date: 2016-03-08 Impact factor: 6.150
Authors: Lindsay E Rhodes; Brandi K Freeman; Sungyoung Auh; Angela D Kokkinis; Alison La Pean; Cheunju Chen; Tanya J Lehky; Joseph A Shrader; Ellen W Levy; Michael Harris-Love; Nicholas A Di Prospero; Kenneth H Fischbeck Journal: Brain Date: 2009-12 Impact factor: 13.501
Authors: Brian D Freibaum; Yubing Lu; Rodrigo Lopez-Gonzalez; Nam Chul Kim; Sandra Almeida; Kyung-Ha Lee; Nisha Badders; Marc Valentine; Bruce L Miller; Philip C Wong; Leonard Petrucelli; Hong Joo Kim; Fen-Biao Gao; J Paul Taylor Journal: Nature Date: 2015-08-26 Impact factor: 49.962