CD98hc is a target for brain delivery of biotherapeutics.

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TVCD98hc). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATVCD98hc) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATVCD98hc demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATVCD98hc that impact FcγR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TVCD98hc as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms.

Using a theoretical approach to predict college students' non-medical use of prescription drugs - a survival analysis.

OBJECTIVES: This study assesses students' non-medical use of prescription drugs (NMUPD) from college entrance to graduation, and examines factors that predict NMUPD. Participants: The study was conducted between May 2011 and September 2015 with 338 students. Methods: Longitudinal cohort study design was used to examine NMUPD across time, and NMUPD-related attitudes and subjective norms. Five yearly interviews were conducted to collect data. Cox proportional hazards regression analysis was used to examine time to NMUPD. Results: Thirty-five percent of study participants reported NMUPD; the majority of those initiated non-medical use before their third year in college. Analyses indicated that more positive attitudes towards NMUPD (HR = 1.73, p < 0.001), increased subjective norms regarding NMUPD (HR = 1.01, p < 0.01), and gender (male) (HR= 1.89, p < 0.001) were significantly associated with sooner NMUPD. Conclusions: Findings suggest that NMUPD prevention efforts that target mutable factors such as attitudes and subjective norms should be implemented early during students' college careers.