Mouse Therapeutic Studies

 

This content area includes all studies that apply any kind of treatment to living whole mice, and that measure efficacy. We define treatment to mean any intervention, even ones that could not plausibly be used as human therapies, to avoid disputes about the practicality of any particular treatment. We define efficacy to mean any property of the animal that has a reasonably clear connection to disease progression or severity.

The content area excludes human trials, studies of non-mouse models, and studies done on cells, brain slices, or other systems that are not whole animals. It excludes studies of genetic effects, e.g., crosses of HD mice with other strains, on the grounds that these are studies of molecular mechanism rather than treatments. It also excludes studies in which the only measurements are molecular on the grounds that these are studies of molecular mechanism rather than efficacy.

Legend and Notes

  • Each row in the table represents one study reported in the given reference: a particular drug or treatment applied to a particular mouse model at a given dosage and route of administration.
  • The icon  indicates that additional information is available by clicking on the icon.
  • In a few cases, we converted actual doses (expressed, e.g., as mg per liter of drinking water) to nominal dose (expressed as mg per kg of body mass) using standard formulas.
  • The start column tells when the drug or treatment was begun. Times are generally in weeks postpartum.
  • The remaining columns report outcome measures. A green + indicates that the paper reports an improvement in that measure; in most cases, we only include outcomes that are described in the paper as being statistically significant; in a few cases, we include outcomes that are near significance or described as being important. A yellow ~ indicates that the paper reports that the measurement was performed, and no significant (or important) improvement was found. A red – indicates that the paper reports that the measurement was performed, and was found to be worse than in the control. A blank indicates that no measurement was reported.
  • Some columns, e.g., ‘Atrophy’, report outcomes from a variety of tests of a general category. The notation is test name followed by ‘+’, ‘~’, or ‘-‘. The absence of a test name indicates that the paper reported no outcome for the test.
  • Note that for some outcomes, an improvement implies that the measure gets bigger, e.g., for survival, while for others the measure gets smaller, e.g., for aggregates.
  • The diabetes column indicates measurements that pertain to diabetic complications often seen in these mouse models.

 

Table

 

Citation Treatment Model Dose Start Outcomes
Survival Weight Behavior Neuropathology Diabetes
Rotarod Other Atrophy Aggregates Other
Wang 2005 siRNA–HDExon1 R6/2 5 μl transfection complex solution birth
+
+
+
other: foot clasping
+
other: open field
+
striatum
+
ventricle
+
striatum
+
Van Raamsdonk 2005 ethyl–EPA YAC128 1% 6.5 months
+
other: open field
+
brain weight
~
neuronal cross-sectional area
~
striatal cell numbers
~
striatal volume
~
other: darpp-32 expression
~
Nguyen 2005 clioquinol R6/2 30 mg/kg/d 3 w
+
+
+
other: foot clasping
+
striatal atrophy
+
+
+
Hunt & Morton 2005 gilbenclamide R6/2 5 mg/kg 5.5 w
~
~
~
+
rosiglitazone 3 mg/kg
~
gilbenclamide & rosiglitazone 5 mg/kg & 3 mg/kg
+
daily repeated exercise (swim tank) 6 days/week 5 w
Hockly 2005 riluzole R6/2 females 0.2 g/l 5 w
~
~
0.4 g/l
other: altered rearing
~
other: grip strength
~
other: progressive hypoactivity
~
brain weight
~
cortex
~
striatum
~
PGL–135 R6/2 0.2 g/l – 0.6 g/l
N/A
Popovic 2005 glial cell line–derived neurotrophic factor (GDNF) R6/2 intrastriatal injection 4-5 w
~
~
clasping
~
groomnig
~
other: open field
~
striatum
~
striatum
~
cell proliferation: dentate gyrus
~
cell proliferation: striatum
~
cell proliferation: subventricular zone
~
Harper 2005 RNA interference (shHD2.1) N171-82Q striatal and cerebellar injection 4 w
~
+
pawprint: stride length
+
cerebellar granule cells
+
striatum
+
Chou 2005 CGS21680 (CGS) R6/2 0.5 μg/g IP 7 w
~
~
~
other: open field
+
striatal neuron
+
2.5 μg/g IP
+
brain weight
+
ventricle
+
5.0 μg/g IP
+
Morton 2005
&
tacrine R6/2 females 2.7 or 3.2 mg/kg/d IP 5 w
+
+
~
t maze
+
water maze: hidden distance
+
water maze: visible 1: thigmotaxis
+
water maze: visible 2: swim speed
water maze: visible 2: thigmotaxis
+
~
+
moclobemide 10 mg/kg/d IP
creatine 1% w/v oral (in diet)
&
tacrine 2.7 or 3.2 mg/kg/d IP
water maze
moclobemide 10 mg/kg/d IP
&
tacrine 2.7 or 3.2 mg/kg/d IP
creatine 1% w/v oral (in diet)
&
moclobemide 10 mg/kg/d IP
creatine 1% w/v oral (in diet)
tacrine 2.7 or 3.2 mg/kg/d IP
+
~
t maze
~
water maze
moclobemide 10 mg/kg/d IP
~
creatine 1% w/v oral (in diet)
Ferrante 2004 mithramycin R6/2 150 μg/kg IP 3 w
+
~
+
brain
+
brain weight
+
~
3-np striatal damage
+
neuronal cell size
+
Diguet 2004 minocycline 3-NP 45 mg/kg IP, twice daily 20 w
beam walking
motor disorder assessment
open field
pole test
striatal neuron
Schiefer 2004 2–methyl–6–(phenylethynyl)–pyridine (MPEP) R6/2 100 mg/kg/d 3.5 w
+
~
+
open field
+
~
~
LY379268 1.2 mg/kg/d
~
open field
+
~
Gardian 2004 phenylbutyrate N171-82Q 100 mg/kg/d IP, 6 days/week (injection volume = 3.33 ml/kg) 75 d
+
~
~
brain
+
ventricle
+
cell loss: striatal neuron
+
Schilling 2004 remacemide N171-82Q 14-17.5 mg/kg 8 w
~
coenzyme Q10 (coQ) 400-500 mg/kg
+
celecoxib 1500 ppm
~
chlorpromazine N171-82Q females 1 mg/kg/day 90 d
~
~
environmental enrichment (EE) exercise, wheels, tubes, social interaction 8 w
~
+
+
Tanaka 2004 trehalose R6/2 0.2% oral 3 w
+
2% oral
+
+
clasping
+
pawprint
+
brain
+
striatum
+
cortex
+
striatum
+
cell loss: cortex
~
cell loss: striatum
~
~
5% oral
Duan 2004 paroxetine N171-82Q 5 mg/kg/day subcutaneous 8 w
+
+
+
ventricle
+
+
13 w
+
Ravikumar 2004 rapamycin ester (CCI–779) N171-82Q 20 mg/kg IP 4 w
~
+
other: grip strength
+
tremors
+
wire maneuver
+
brain weight
striatum
+
Zucker 2004 gabapentin (GBP) R6/2 100 mg/kg/d 6 w
~
beam walking
~
~
~
gabapentin–lactam (GBP–L) 100 mg/kg/d
beam walking
+
hippocampus
+
neocortex
+
striatum
+
Spires 2004 environmental enrichment (EE) R6/1 variety of non-toxic objects were placed in the home cage and changed every 2 days 4 w
+
+
brain weight
~
Dedeoglu 2003 creatine R6/2 2% oral 6 w
+
+
+
brain weight
+
striatum
+
striatum
+
cell loss: striatal neuron
+
8 w
~
brain
~
striatum
~
striatum
~
10 w
~
~
striatum
~
Klivenyi 2003 BN82451 R6/2 30mg/kg/d 30 d
+
~
+
striatum
+
striatum
+
cell loss: striatal neuron
+
Hockly 2003 suberoylanilide hydroxamic acid (SAHA) R6/2 100 mg/kg 30 d
+
other: grip strength
~
~
~
Ferrante 2003 sodium butyrate R6/2 females 100 mg/kg/d 3 w
~
~
200 mg/kg/d
+
400 mg/kg/d
+
600 mg/kg/d
1200 mg/kg/d
+
brain weight
+
striatum
~
3-np striatal damage
+
cell loss: striatal neuron
+
5000 mg/kg/d
10000 mg/kg/d
Smith 2003 minocycline R6/2 1 mg/ml 4 w
~
~
other: grip strength
~
5 mg/ml
~
+
doxycycline 2 mg/ml
6 mg/ml
~
+
Miller 2003 DNA vaccine R6/2 females 100 μg plasmid, 2 doses 2 w apart 5 w
~
general
~
+
Wood 2003 lithium R6/2 16 mg/kg/d 5.3 w
~
~
10.5 w
+
+
S�nchez 2003 congo red R6/2 not stated 9 w
+
pawprint
+
hippocampus
+
+
1 mg/30 g/2d IP
+
+
hind limb clasping
+
basal ganglia
+
168 mg/28d ICV pump
Duan 2003 dietary restriction (DR) N171-82Q fast every other day 8 w
+
+
+
onset limb tremors
+
ventricle
+
cortex
+
striatum
+
+
Ferrante 2002 coenzyme Q10 (coQ) R6/2 400-500 mg/kg 3 w
+
+
+
brain
+
striatum neuron
+
remacemide 14-17.5 mg/kg
&
coenzyme Q10 (coQ) 400-500 mg/kg
+
brain
+
striatum neuron
+
ventricle
+
striatum
+
remacemide 14-17.5 mg/kg
&
coenzyme Q10 (coQ) N171-82Q 400-500 mg/kg
+
remacemide 14-17.5 mg/kg
Keene 2002 tauroursodeoxycholic acid (TUDCA) R6/2 500mg/kg/3d SC 6 w
+
open field
+
cerebrum
+
striatum
+
striatum
+
Dedeoglu 2002 cystamine R6/2 112 mg/kg IP 3 w
+
+
+
brain
+
striatum neuron
+
cortex
+
striatum
+
225 mg/kg IP
225 mg/kg oral prenatal
Karpuj 2002 cystamine R6/2 1 μmol/d IP 7 w
+
+
clasping
+
pawprint
+
cortex
~
hippocampus
~
striatum
~
~
Clifford 2002 essential fatty acids (EFA) R6/1 254 mg/2d prenatal
+
~
clasping
+
ethologic
+
Schiefer 2002 riluzole R6/2 10 mg/kg/d 3 w
+
+
~
hyperactivity phase
+
open field
+
cerebral cortex
~
striatum
~
~
Hockly 2002 environmental enrichment (EE) R6/2 cardboard tube in cage 4 w
~
+
other: grip strength
+
brain
~
peristriatum
~
striatum
~
anterior cingulate cortex
~
striatum
~
bigger cage, more mice per cage, more bedding materials, toys
+
brain
~
peristriatum
+
striatum
~
Schilling 2001
&
coenzyme Q10 (coQ) N171-82Q 400-500 mg/kg 4-8 w
~
+
+
cerebellar granule cells
~
remacemide 14-17.5 mg/kg
Andreassen 2001 creatine N171-82Q 100 mg/d 4 w
+
+
+
brain
+
striatum
+
striatum neuron
+
cortex
+
striatum
+
+
Andreassen 2001 lipoic acid R6/2 100 mg/kg/d
~
N171-82Q
+
2–sulpho–tert–phenyibutyinitrone (S–PBN) R6/2 120mg/kg/d
~
~
Andreassen 2001 dichloroacetate (DCA) 100 mg/kg/d
+
+
+
striatum neuron
+
~
+
N171-82Q
Ende 2001 human umbilical cord blood (HUBC) R6/2 71-74 x 10^6
+
+
100-105 x 10^6
+
van Dellen 2001 cortical transplantation R6/1 newborn
clasping
+
horizontal bar
~
striatum
~
Ferrante 2000 creatine R6/2 50 mg/d 3 w
+
+
+
100 mg/d
+
+
+
striatum
+
striatum neuron
+
cortex
~
striatum
+
+
150 mg/d
+
+
+
Chen 2000 minocycline R6/2 5 mg/kg IP 6 w
+
~
+
brain
+
~
zVAD–fmk 100 mg /20 g/28d ICV pump 7 w
YVAD–cmk 50 mg /20 g/28d ICV pump
~
DEVD–fmk
&
YVAD–cmk
+
+
DEVD–fmk
Carter 2000 environmental enrichment (EE) R6/2 enhanced diet 4 w
+
+
clasping
~
ethologic
+
open field
~
enhanced diet + mixed housing with WT mice
+
enhanced diet + early weaning +behavioral testing 2.5 w
~
enhanced diet + allowed to breed 4 w
van Dellen 2000 environmental enrichment (EE) R6/1 cardboard, paper, plastic objects 4 w
~
clasping
+
horizontal bar
+
peristriatum
+
striatum
~
striatum
~
Ona 1999 zVAD–fmk R6/2 100 mg /20 g/28d ICV pump 7 w
+
+
Dunnett 1998 striatal transplantation R6/2 10 w
~
open field
+