Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice.
Huntington's disease (HD) is a fatal neurodegenerative disorder of genetic origin with no known therapeutic intervention that can slow or halt disease progression. Transgenic murine models of HD have significantly improved the ability to assess potential therapeutic strategies. The R6/2 murine model of HD, which recapitulates many aspects of human HD, has been used extensively in pre-clinical HD therapeutic treatment trials. Of several potential therapeutic candidates, both minocycline and coenzyme Q10 (CoQ10) have been demonstrated to provide significant improvement in the R6/2 mouse. Given the specific cellular targets of each compound, and the broad array of abnormalities thought to underlie HD, we sought to assess the effects of combined minocycline and CoQ10 treatment in the R6/2 mouse. Combined minocycline and CoQ10 therapy provided an enhanced beneficial effect, ameliorating behavioral and neuropathological alterations in the R6/2 mouse. Minocycline and CoQ10 treatment significantly extended survival and improved rotarod performance to a greater degree than either minocycline or CoQ10 alone. In addition, combined minocycline and CoQ10 treatment attenuated gross brain atrophy, striatal neuron atrophy, and huntingtin aggregation in the R6/2 mice relative to individual treatment. These data suggest that combined minocycline and CoQ10 treatment may offer therapeutic benefit to patients suffering from HD.
Stack
Edward C
EC
Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, MA 01730, USA.
Smith
Karen M
KM
Ryu
Hoon
H
Cormier
Kerry
K
Chen
Minghua
M
Hagerty
Sean W
SW
Del Signore
Steven J
SJ
Cudkowicz
Merit E
ME
Friedlander
Robert M
RM
Ferrante
Robert J
RJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003067:Coenzymes; D019610:Cytoprotection; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D015996:Survival Rate; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D003067:Coenzymes; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014451:Ubiquinone; C024989:coenzyme Q10; D008911:Minocycline