Aripiprazole for the treatment of irritability associated with autism

INTRODUCTION: Irritability (including tantrums, aggression and moodiness) is often associated with autistic disorder. Children with autism are frequently prescribed atypical antipsychotic medications for these behaviors. Although multiple agents have been found to be effective, the safety and tolerability of each antipsychotic may be the determining factor in its selection. AREAS COVERED: The pharmacokinetics, pharmacodynamics, safety and efficacy data on aripiprazole for the treatment of irritability associated with autism are discussed. Knowledge of the mechanism of action, advantages and disadvantages relative to other atypical antipsychotics, and an appreciation of the efficacy of aripiprazole when used to treat irritability in autism is also explored in this paper. EXPERT OPINION: Aripiprazole may have a more favorable side-effect profile than another commonly prescribed medication, risperidone, because of its unique mechanism of action. It seems to be effective in treating irritability associated with autism, but more research is needed.     

Nanomedicine in cancer therapy: innovative trends and prospects

Cancer is a leading cause of morbidity and mortality worldwide, with recent advancements resulting in modest impacts on patient survival. Nanomedicine represents an innovative field with immense potential for improving cancer treatment, having ushered in several established drug delivery platforms. Nanoconstructs such as liposomes are widely used in clinics, while polymer micelles are in advanced phases of clinical trials in several countries. Currently, the field of nanomedicine is generating a new wave of nanoscale drug delivery strategies, embracing trends that involve the functionalization of these constructs with moieties that enhance site-specific delivery and tailored release. Herein, we discuss several advancements in established nanoparticle technologies such as liposomes, polymer micelles, and dendrimers regarding tumor targeting and controlled release strategies, which are being incorporated into their design with the hope of generating a more robust and efficacious nanotherapeutic modality. We also highlight a novel strategy known as multistage drug delivery; a rationally designed nanocarrier aimed at overcoming numerous biological barriers involved in drug delivery through the decoupling of various tasks that comprise the journey from the moment of systemic administration to arrival at the tumor site.     

Virus-tumor interactome screen reveals ER stress response can reprogram resistant cancers for oncolytic virus-triggered caspase-2 cell death

To identify therapeutic opportunities for oncolytic viral therapy, we conducted genome-wide RNAi screens to search for host factors that modulate rhabdoviral oncolysis. Our screens uncovered the endoplasmic reticulum (ER) stress response pathways as important modulators of rhabdovirus-mediated cytotoxicity. Further investigation revealed an unconventional mechanism whereby ER stress response inhibition preconditioned cancer cells, which sensitized them to caspase-2-dependent apoptosis induced by a subsequent rhabdovirus infection. Importantly, this mechanism was tumor cell specific, selectively increasing potency of the oncolytic virus by up to 10,000-fold. In?vivo studies using a small molecule inhibitor of IRE1α showed dramatically improved oncolytic efficacy in resistant tumor models. Our study demonstrates proof of concept for using functional genomics to improve biotherapeutic agents for cancer.