Background: Gantenerumab is a fully human anti-A␤ monoclonal antibody in clinical development for the treatment of Alzheimer disease (AD). Objectives: To investigate whether treatment with gantenerumab leads to a measurable reduction in the level of A␤ amyloid in the brain and to elucidate the mechanism of amyloid reduction. Design: A multicenter, randomized, double-blind, placebo-controlled, ascending-dose positron emission tomographic study. Additionally, ex vivo studies of human brain slices from an independent sample of patients who had AD were performed.

To evaluate the effect of intermittent hypoxemia on neuropsychological functioning, neuropsychological tests were administered to 14 sleep apnea patients, a control group of 10 patients with other disorders of excessive somnolence, and another control group of 14 healthy volunteers. The sleep disorder groups were matched on two measures of sleepiness. It was found that sleep apnea patients performed significantly worse than both controls on 7 of 14 neuropsychological measures and on a rating of global neuropsychological impairment. The overall level of performance reflected only moderate impairment. Within the sleep apnea group, hypoxemia severity was significantly correlated with deficits on measures of motor and perceptual-organizational ability.

clinicaltrials.gov Identifier: NCT01437657.

Preclinical data suggest that inhibition of the metabotropic glutamate receptor 5 (mGluR5) receptor might hold therapeutic benefits in Fragile X syndrome (FXS). Treatment of Fmr1 knockout mice with mGluR5-negative allosteric modulators (NAMs) has been reported to correct a broad range of phenotypes related to FXS. The early short-term clinical trials with mGluR5 NAMs, including basimglurant, assessing the effects in individuals with FXS, were supportive of further exploration in larger, well-controlled trials. We evaluated basimglurant, a potent and selective mGluR5 NAM, in a 12-week, double-blind, parallel-group study of 183 adults and adolescents (aged 14–50, mean 23.4 years) with FXS. Individuals with an FMR1 full mutation were randomized to placebo or one of two doses of basimglurant. The primary efficacy endpoint was the change from baseline in behavioral symptoms using the Anxiety Depression and Mood Scale (ADAMS) total score. All treatment arms showed marked behavioral improvements from baseline to week 12 with less improvement in the basimglurant 1.5 mg arm than placebo; however, basimglurant 0.5 mg was inferior to placebo in the ADAMs total score. Treatment with basimglurant was overall well-tolerated. A higher incidence of adverse events classified as psychiatric disorders were reported in patients treated with basimglurant, including three patients with hallucinations or psychosis. In this phase 2 clinical trial, basimglurant did not demonstrate improvement over placebo. Evaluation of the overall risk-benefit in younger patient populations is an important consideration for the design of potential further investigations of efficacy with this class of medications.

Tolcapone was well tolerated and substantially increased on time and reduced off time in patients with fluctuating Parkinson disease. Additionally, levodopa requirements were significantly decreased.