Therapeutic Effects of Coenzyme Q10 and Remacemide in Transgenic Mouse Models of Huntington's Disease

@article{Ferrante2002TherapeuticEO,
  title={Therapeutic Effects of Coenzyme Q10 and Remacemide in Transgenic Mouse Models of Huntington's Disease},
  author={Robert J. Ferrante and Ole Andreas Andreassen and Alpaslan Dedeoglu and Kimberly L. Ferrante and Bruce G. Jenkins and Steven M. Hersch and M. Flint Beal},
  journal={The Journal of Neuroscience},
  year={2002},
  volume={22},
  pages={1592 - 1599}
}
There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neurodegenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q10 and the NMDA antagonist remacemide. We found that oral administration of either coenzyme Q10 or remacemide significantly extended survival and delayed… 
Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington's disease mice.
TLDR
It is demonstrated that high-dose administration of CoQ10 exerts a greater therapeutic benefit in a dose dependent manner in R6/2 mice than previously reported and suggested that clinical trials using high dose CoQ 10 in HD patients are warranted.
Therapeutic effects of coenzyme Q10 in neurodegenerative diseases.
  • M. Beal
  • Medicine
    Methods in enzymology
  • 2004
TLDR
The initial results of utilizing CoQ 10 administration for treatment of neurodegenerative disease appear promising as a treatment to slow the inexorable progression of these disorders.
Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice.
TLDR
Combined minocycline and CoQ10 therapy provided an enhanced beneficial effect, ameliorating behavioral and neuropathological alterations in the R6/2 mouse, suggesting that combined minocy cline and coenzyme Q10 treatment may offer therapeutic benefit to patients suffering from HD.
Behavioral improvement after chronic administration of coenzyme Q10 in P301S transgenic mice.
TLDR
The data show that coenzyme Q10 significantly improved behavioral deficits and survival in transgenic mice with the P301S tau mutation, upregulated key enzymes of the electron transport chain, and reduced oxidative stress.
Combination therapy with Coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases
TLDR
The findings suggest that combination therapy using CoQ10 and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson’s disease and HD.
Therapeutic Effects of Cystamine in a Murine Model of Huntington's Disease
TLDR
Treatment in R6/2 transgenic HD mice, using the transglutaminase inhibitor cystamine, significantly extended survival, improved body weight and motor performance, and delayed the neuropathological sequela.
Coenzyme Q10 effects in neurodegenerative disease
TLDR
CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy, and Phase III trials of high-dose CoQ10 in large sample sizes are needed to further ascertain the effects of CoQ 10 in neurodegenerative diseases.
Evidence for behavioral benefits of early dietary supplementation with CoEnzymeQ10 in a slowly progressing mouse model of Huntington's disease
TLDR
Data confirm that CoQ10 may be beneficial in HD but suggest that maximum benefit may be observed when treatment is begun at early stages of the disease and that dosage may be critical.
Neuroprotective Effects of Phenylbutyrate in the N171-82Q Transgenic Mouse Model of Huntington's Disease*
TLDR
Results show that administration of phenylbutyrate, at doses that are well tolerated in man, exerts significant neuroprotective effects in a transgenic mouse model of HD, and therefore represents a very promising therapeutic approach for HD.
Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse model of Huntington’s disease
TLDR
A novel KYNA analogue exhibited several significant effects: it prolonged the survival of the transgenic mice, ameliorated their hypolocomotion, prevented the loss of weight and completely prevented the atrophy of the striatal neurons in Huntington’s disease.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 58 REFERENCES
Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease
TLDR
Nuclear magnetic resonance spectroscopy showed that creatine supplementation significantly increased brain creatine concentrations and delayed decreases in N-acetylaspartate concentrations, supporting a role of metabolic dysfunction in a transgenic mouse model of HD and suggesting a novel therapeutic strategy to slow the pathological process.
Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates.
TLDR
Findings show that chronic administration of 3-NP to nonhuman primates can replicate many of the characteristic motor and histologic features of HD, further strengthening the possibility that a subtle impairment of energy metabolism may play a role in its pathogenesis.
Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid
TLDR
It is demonstrated that lesions due to quinolinic acid closely resemble those of HD as they result in marked depletions of both GABA and substance P, with selective sparing of somatostatin/neuropeptide Y neurones.
Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity.
TLDR
It is proposed that the presence of exon 1 of the mutant HD gene induces profound changes in striatal neurons that render these cells resistant to excessive NMDA receptor activation.
Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease
TLDR
Evidence of caspase-1 activation in the brains of mice and humans with Huntington's disease is demonstrated and it is demonstrated that intracerebroventricular administration of a casp enzyme inhibitor delays disease progression and mortality in the mouse model of Huntington’s disease.
Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate
TLDR
The results confirm that mitochondrial toxins produce striatal excitotoxic lesions by a mechanism involving energy depletion in vivo and suggest novel neuroprotective strategies that may be useful in the treatment of both mitochondrial encephalopathies and neurodegenerative diseases.
Energy metabolism defects in Huntington's disease and effects of coenzyme Q10
TLDR
Evidence for a generalized energy defect in Huntington's disease is provided, and a possible therapy is suggested to treat patients with coenzyme Q10.
Antiglutamate therapies in Huntington's disease.
  • K. Kieburtz
  • Medicine
    Journal of neural transmission. Supplementum
  • 1999
TLDR
A current, NIH-funded trial of remacemide hydrochloride and Coenzyme Q10 in 340 patients with Huntington's disease is described, which is the largest and longest multi-center trial to address the glutamate- and mitochondrial-mediated hypotheses of neurodegeneration.
Mitochondrial defect in Huntington's disease caudate nucleus
TLDR
The mitochondrial defect identified in HD caudate parallels that induced by HD neurotoxin models and further supports the role of abnormal energy metabolism in HD.
Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy.
TLDR
Lactate concentrations were increased in the occipital cortex of symptomatic HD patients when compared with normal controls, and the lactate level correlated with duration of illness, consistent with a possible defect in energy metabolism in HD.
...
1
2
3
4
5
...