Evaluation of tetrathiomolybdate in the R6/2 model of Huntington disease.
Huntington disease is an uncommon autosomal dominant neurodegenerative disorder caused by expanded polyglutamine repeats in the huntingtin protein. The proximate mechanisms responsible for neurodegeneration are unknown. Copper ions may play a role in Huntington disease by promoting oligomerization of expanded polyglutamine repeat protein fragments. Ammonium tetrathiomolybdate is a copper complexing agent with demonstrated tolerability and efficacy in another neurodegenerative disorder, Wilson disease. We evaluated ammonium tetrathiomolybdate in the R6/2 transgenic mouse model of Huntington disease. Ammonium tetrathiomolybdate treatment delayed the onset of motor dysfunction in R6/2 mice. There was a trend towards reduced striatal degeneration, suggesting a neuroprotective effect of ammonium tetrathiomolybdate in this model. Given its known tolerability in humans with neurodegeneration, ammonium tetrathiomolybdate could be considered as a candidate for clinical trials in Huntington disease.
Tallaksen-Greene
Sara J
SJ
Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Janiszewska
Anita
A
Benton
Kasha
K
Hou
Guoqing
G
Dick
Robert
R
Brewer
George J
GJ
Albin
Roger L
RL
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045586:Intranuclear Inclusion Bodies / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008982:Molybdenum / Q000378:metabolism*; D009043:Motor Activity / Q000235:genetics; D011930:Reaction Time / Q000235:genetics; D015996:Survival Rate
D008982:Molybdenum; C020809:tetrathiomolybdate