Japanese physicians' attitudes towards enteral nutrition treatment for pediatric patients with Crohn's disease: a questionnaire survey

Background/Aims: Enteral nutrition (EN) is recommended for the treatment of pediatric Crohn's disease (CD) in Japan. However, the indications and treatment protocols for EN vary among hospitals. In the present study, we aimed to determine how EN was administered to pediatric patients and whether physicians followed treatment guidelines in their practices.Methods: Two types of questionnaires were administered to 32 physicians who were involved in the treatment of pediatric CD. The consensus questionnaire evaluated the physicians' attitudes towards EN, whereas the efficacy questionnaire collected data on patients with CD, aged <17 years, who had undergone induction therapy between 2006 and 2011.Results: A total of 23 physicians responded to the questionnaires. The results of the consensus questionnaire indicated that 82% and 59% of study participants recommended EN treatment for all newly diagnosed pediatric patients with CD and all relapsed patients, respectively. Exclusive EN (EEN) and elemental formula were recommended by 84% and 85% of physicians, respectively. The efficacy questionnaire revealed that 57 of the 58 patients received EN. Elemental formula was used in 39 of 40 patients who were treated with EEN. Of these 40 patients, 27 were treated with EEN alone; of these, 22 (81%) achieved remission without any other treatment. The mean duration of EEN was 15.9 days.Conclusions: EN is widely recommended by physicians treating pediatric CD in Japan. In contrast to Western countries, clinicians used elemental formula more often and with a shorter EEN treatment duration

Enzyme replacement with transferrin receptor-targeted α-L-iduronidase rescues brain pathology in mucopolysaccharidosis I mice

Mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by dysfunction of α-L-iduronidase (IDUA), is characterized by the deposition of dermatan sulfate (DS) and heparan sulfate (HS) throughout the body, which causes several somatic and central nervous symptoms. Although enzyme-replacement therapy (ERT) is currently available to treat MPS I, it does not alleviate central nervous disorders, as it cannot penetrate the blood-brain barrier. Here we evaluate the brain delivery, efficacy, and safety of JR-171, a fusion protein comprising humanized anti-human transferrin receptor antibody Fab and IDUA, using monkeys and MPS I mice. Intravenously administered JR-171 was distributed in major organs, including the brain, and reduced DS and HS concentrations in the central nervous system and peripheral tissues. JR-171 exerted similar effects on peripheral disorders similar to conventional ERT and further reversed brain pathology in MPS I mice. We found that JR-171 improved spatial learning ability, which was seen to deteriorate in the vehicle-treated mice. Further, no safety concerns were noted in repeat-dose toxicity studies in monkeys. This study provides nonclinical evidence that JR-171 might potentially prevent and even improve disease conditions in patients with neuronopathic MPS I without serious safety concerns