Target occupancy study and whole-body dosimetry with a MAGL PET ligand [C]PF-06809247 in non-human primates.

Background: Monoacylglycerol lipase (MAGL) is a key serine hydrolase which terminates endocannabinoid signaling and regulates arachidonic acid driven inflammatory responses within the central nervous system. To develop [C]PF-06809247 into a clinically usable MAGL positron emission tomography (PET) radioligand, we assessed the occupancy of MAGL by an inhibitor in the non-human primate (NHP) brain. Additionally, we measured the whole-body distribution of [C]PF-06809247 in NHP and estimated human effective radiation doses.

Sleep Behaviors and Handedness in Gifted and Non-Gifted Children.

Patterns of sleep behaviors appear to differ across students with special needs including those classified with developmental disorders, attention-deficit/hyperactivity disorder, and autism. One understudied segment of the special needs population is that of gifted children, students who bring their own unique set of behavioral characteristics. In the present study, it was hypothesized that because of unique cognitive and socio-emotional intensities, gifted children would experience elevated levels of sleep disturbance in comparison to their non-gifted peers.

Microglial Drug Targets in AD: Opportunities and Challenges in Drug Discovery and Development.

Alzheimer's disease (AD) is a large and increasing unmet medical need with no disease-modifying treatment currently available. Genetic evidence from genome-wide association studies (GWASs) and gene network analysis has clearly revealed a key role of the innate immune system in the brain, of which microglia are the most important element. Single-nucleotide polymorphisms (SNPs) in genes predominantly expressed in microglia have been associated with altered risk of developing AD.

Identification and Development of an Irreversible Monoacylglycerol Lipase (MAGL) Positron Emission Tomography (PET) Radioligand with High Specificity.

Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Preclinically, inhibition of MAGL is known to provide therapeutic benefits for a number of neurological disorders. The availability of a MAGL-specific positron emission tomography (PET) ligand would considerably facilitate the development and clinical characterization of MAGL inhibitors via noninvasive and quantitative PET imaging.