HD Lighthouse Contributing Editor's Comment: We have achieved a milestone in HD research: the first study to demonstrate an additive effect in a combination trial with HD mice. Minocycline and CoQ10 were administered separately and together to R6/2 mice and the results were compared to untreated mice and normal mice (5 groups total). Mice treated with minocycline alone survived 11.2 percent longer than the untreated mice. The CoQ10 group survived 14.6 longer and the minocycline/CoQ10 group survived 18.2 percent longer. Similarly, both minocycline and CoQ10 separately improved rotarod performance with combined treatment yielding the best results.

Minocycline treated mice experienced less striatum and less overall brain volume loss compared to untreated R6/2 mice. CoQ10 treated mice did even better than the minocycline treated mice with comparable results for the mice treated with both (no additive effect on these measures).

The body weight of mice treated with CoQ10 but not minocycline was greater than the untreated mice. The combination results were comparable to CoQ10 alone. A pathological feature in the R6/2 mice as well as HD patients is reactive microglia (an immune system response of the brain). This reaction was reduced in the minocycline group but not the CoQ10 group with comparable results in the combined treatment group.

Clearly then, the R6/2 mice benefited most from receiving both treatments. The authors conclude, "Given the complexities that underlie the pathogenesis of HD, a therapeutic strategy that employs combined treatments that target separate pathologies is likely to provide the most beneficial improvement. The fact that both compounds have already been safely assessed in HD patients, their combined use may provide potential added benefit."
--Marsha L. Miller, Ph.D.
Posted to the HDL: 12 Dec 2005

Combination Therapy Using Minocycline and Coenzyme Q10 in R6/2 transgenic Huntington's Disease Mice

Stack, Smith, Ryu, Cormier, Chen, Hagerty, Del Signore, Cudkowicz, Friedlander, and Ferrante

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.

Tracked on the Lighthouse:
minocycline
CoQ10

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Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Dec 5, 2005.

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