The novel substituted pyrimidine, KP544, reduces motor deficits in the R6/2 transgenic mouse model of Huntington's disease.
OBJECTIVE
The purpose of this study was to test the potential therapeutic effects of the substituted pyrimidine, KP544, which has been shown to amplify the effects of nerve growth factor in vitro, on motor deficits in the R6/2 transgenic mouse model of Huntington's disease (HD).


METHODS
Young, female R6/2 mice were given daily oral intubation of either 10 mg/kg KP544 or vehicle (0.5% methylcellulose) at 6 weeks of age and tested from postnatal weeks 8 through 12 on a battery of motor tasks, including assessments of clasping (drawing of the limbs to the torso when suspended by the tail), motor coordination on the rotarod, and spontaneous motor activity in the open-field. Following testing, the mice were sacrificed and the brains were sectioned and stained with cresyl violet for histological examination.


RESULTS
KP544 treatment decreased balance deficits on the rotarod task, reduced clasping, delayed the onset of hypoactivity, and reduced enlargement of the lateral ventricles in R6/2 mice.


CONCLUSIONS
These results suggest that KP544 can reduce motor deficits and anatomical alterations in R6/2 mice. Further research into the use of KP544 as a potential pharmacotherapy HD is warranted.
Dey
Nicholas D
ND
Field Neurosciences Laboratory for Restorative Neurology, Department of Psychology and Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48858, USA.
Boersen
Angela J
AJ
Myers
Rebecca A
RA
York
Lynae R
LR
Bombard
Matthew C
MC
Lu
Ming
M
Sandstrom
Michael I
MI
Hulce
Verne D
VD
Lescaudron
Laurent
L
Dunbar
Gary L
GL
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003511:Cyclohexanols / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006816:Huntington Disease / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D009154:Mutation; D011743:Pyrimidines / Q000627:therapeutic use*; D011930:Reaction Time
C514429:2-amino-5-(4-chlorophenylethynyl)-4-(4-hydroxycyclohexylamino)pyrimidine; D003511:Cyclohexanols; D011743:Pyrimidines