IDEBENONE - A REVIEW OF ITS USE IN MILD-TO-MODERATE ALZHEIMERS-DISEASE

Idebenone is a benzoquinone derivative which is structurally related t o ubiquinone, a component of the respiratory chain. Although the preci se mechanism of action of the drug is unknown, preclinical studies sug gest that idebenone amy exert cytoprotective properties by acting as a free radical scavenger. In addition, it also appears to improve cereb ral metabolism, correct neurotransmitter defects and enhance memory an d learning. Oral idebenone appears to improve cognitive function and b ehavioural deficits in patients with mild to moderate Alzheimer's dise ase. In 2 large double-blind placebo-controlled trials, idebenone 270 or 360 mg/day for up to 12 months produced a mean improvement of 1.6 t o 3.9 points in the total score of the Alzheimer's Disease Assessment Scale (ADAS-Total) relative to placebo. After 12 months of treatment, improvements in ADAS-Total versus baseline were 10.3% with placebo, 14 .7% with idebenone 270 mg/day and 19.6% with idebenone 360 mg/day. 34. 1% of patients treated with idebenone 360 mg/day were judged to have i mproved when assessed according to measures of cognition, behaviour an d clinician-rated global outcome measures. Notably, patients with a le sser degree of cognitive impairment (ADAS-Total <20) appear less likel y to benefit from idebenone therapy. Idebenone was well tolerated when administered for up to 12 months to patients with Alzheimer's disease , and no significant changes in vital signs or laboratory values were reported. Thus, although comparisons with other agents are currently l acking, available data suggest the idebenone will be a useful therapeu tic option for the management of Alzheimer's disease. Because of their different mechanisms of actions, combination therapy with idebenone a nd a cholinesterase inhibitor may also be a possibility in the future. However, studies are necessary to assess the feasibility of such an a pproach for the treatment of Alzheimer's disease.