Sustained efficacy and safety of idebenone in the treatment of Alzheimer’s disease: update on a 2-year double-blind multicentre study

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

“…While CoQ supplementation has benefit in persons with CoQ synthesis disorders and in preclinical mouse models of AD, it is ineffective as a therapeutic in persons with AD [32,65,83]. In a randomized, double-blind, multicenter study with 450 participants with mild-to-moderate AD, Idebenone showed minimal cognitive benefit [69][70][71], but was not approved for treatment of AD based on results not reaching statistical significance in larger trials [70][71][72]. Methylene blue can enhance cytochrome c oxidase activity through direct electron donation [80,81].…”

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…Recent studies have shown the CoQ 10 to be neuroprotective in various conditions but mostly in in vitro and in vivo animal models (as reviewed by Bonda et al 2010, andWallen 2010), as until now the only clinical trial with CoQ 10 monotherapy was a double-blind, placebo controlled study on AD patients (N=78) treated 16 week with or with 400 mg of CoQ 10 3 times/d, in which no effect on cognition and cerebrospinal antioxidant biomarkers were found (Galasko et al 2012). Additionally, a synthetic variant of CoQ 10 , idebenone, has been tested in clinical trials in which inconsistent results were obtained; better cognitive score in with 90 -120 mg doses only (Gutzmann et al 1998;Weyer et al 1997) and no effect with even higher doses in another trial . Contrary to that, neuroprotective effect of CoQ 10 was clearly demonstrated both at the cognitive and neurochemical level in the STZ-icv rat sAD model (Ishrat et al 2006).…”

Antioxidants and Alzheimer's disease: time to stop feeding vitamin E to dementia patients?

“…The drug has been assessed in two randomized trials of 6 and 12 months' duration respectively (Gutzmann et al, 1996;Gutzmann and Hadler, 1998). The first trial randomized 300 AD patients, the second 450, and in both trials two-thirds of those randomized received various doses of active drug and one-third were treated with placebo.…”

“…The first trial randomized 300 AD patients, the second 450, and in both trials two-thirds of those randomized received various doses of active drug and one-third were treated with placebo. The second study also incorporated a 12-month extension in which all patients received idebenone (Gutzmann and Hadler, 1998). Both trials showed a robust, statistically significant dose-dependent beneficial effect of the drug on both standard measures of cognition and clinical global impression of change.…”

“…Idebenone was reported to be well tolerated with no significant disadvantage over placebo in terms of reported adverse events. The drug's beneficial effects continued into a second year of treatment (Gutzmann and Hadler, 1998). It is therefore disappointing and mysterious that further reports of clinical development of idebenone to treat AD over the past eight years are lacking.…”