Aripiprazole in the real-world treatment for irritability associated with autism spectrum disorder in children and adolescents in Japan: 52-week post-marketing surveillance.

BACKGROUND: The purpose of this study was to evaluate the post-marketing safety and effectiveness of aripiprazole in treating irritability in pediatric patients (6-17 years) with autism spectrum disorder (ASD) in actual clinical sites of Japan. METHODS: In this post-marketing surveillance, patients were enrolled into the multicenter, prospective, non-interventional, observational study for 52 weeks, and were dosed with aripiprazole (1-15 mg/day) under daily clinical settings in Japan. RESULTS: In 510 patients, the continuation rate of aripiprazole treatment was 84.6% at day 168 (week 24) and 78.1% at day 364 (week 52). Adverse drug reactions (ADRs) occurred in 22.7% of patients (n = 116), and the most common ADRs were somnolence (9.4%), followed by weight increased (3.3%). At week 4, the mean change from baseline in the irritability subscale score for the Aberrant Behavior Checklist Japanese version (ABC-J) was - 5.7 ± 6.8 (n = 288). Based on multiple regression analysis, comorbid attention deficit and hyperactivity did not affect the ABC-J irritability subscale score at endpoint. At week 24, the mean change from baseline for the Strengths and Difficulties Questionnaire was - 3.3 ± 4.9 (n = 215) for the total difficulties score and 0.6 ± 1.7 (n = 217) for the prosocial behavior subscale score. CONCLUSIONS: Aripiprazole was well tolerated and effective in the long-term treatment of irritability associated with ASD in Japanese pediatric patients in the real-world clinical practice. TRIAL REGISTRATION: This surveillance was registered with Clinical Trial.gov (no. NCT03179787 ) on June 7, 2017 (retrospectively registered).

Prediction of intracellular targets of a small compound by analyzing peptides presented on MHC class I.

In chemical biology, the elucidation of chemical target is crucial for successful drug development. Because MHC class I molecules present peptides from intracellular damaged proteins, it might be possible to identify targets of a chemical by analyzing peptide sequences on MHC class I. Therefore, we treated cells with the autophagy-inducing chemical TMD-457 and identified the peptides presented on MHC class I. Many of the peptides were derived from molecules involved in ER trafficking and ER stress, which were confirmed by morphological and biochemical analyses. Therefore, our results demonstrate that analyzing MHC class I peptides is useful for the detection of chemical targets.

The expression of anamorsin in diffuse large B cell lymphoma: possible prognostic biomarker for low IPI patients.

Anamorsin is a cell-death-defying factor, which was originally isolated as a molecule that conferred resistance to apoptosis induced by growth factor starvation. In order to evaluate anamorsin expression levels in malignant lymphoma, we immunostained paraffin-embedded sections with anti-anamorsin monoclonal antibodies. About 40% (89/234) of sections from patients with diffuse large B cell lymphoma (DLBCL) showed strong anamorsin expression. Comparing the level of anamorsin expression in DLBCL patients with their clinical features (i.e., overall survival rate, International Prognostic Index (IPI) parameters, and treatment response) revealed no significant correlation between anamorsin expression levels and these clinical features. However, anamorsin expression in DLBCL patients with a low IPI was shown to be an unfavorable biomarker, especially in the patients who received chemotherapy without rituximab. It is suggested that anamorsin might play some roles in the abnormal growth of DLBCL.