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30 Dec 2019

Current And Emerging Therapies For Managing Hyperphagia And Obesity In Prader‐Willi syndrome: A Narrative Review

Hein Min Tun published in Obesity Reviews, with collaborators from Department of Pediatrics, Department of Agricultural, Food and Nutritional ScienceUniversity of Alberta, a review on the pathogenesis of Prader-Willi syndrome to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain.

>>> Current And Emerging Therapies For Managing Hyperphagia And Obesity In Prader‐Willi syndrome: A Narrative Review

Tan Q, Orsso CE, Deehan EC, Triador L, Field CJ, Tun HM, Han JC, Müller TD, Haqq AM.

PMID: 31889409 DOI: 10.1111/obr.12992

Summary

In early childhood, individuals with Prader‐Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: “PWS” AND “therapy” OR “[drug name]”; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long‐term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off.
 

10 Dec 2019

Cross-reactive antibody-dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission

Sophie Valkenburg published in Clinical & Translational Immunology a new paper: Cross-reactive antibody-dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission with Malik Peiris, Benjamin Cowling, Leo Poon and colleagues from the School of Public Health.

>>> Cross-reactive antibody-dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission

Sophie A Valkenburg , Vicky J Fang, Nancy HL Leung , Daniel KW Chu, Dennis KM Ip, Ranawaka APM Perera, Yizhuo Wang, Athena PY Li, JS Malik Peiris, Benjamin J Cowling & Leo LM Poon.

PMID: 31763042 PMCID: PMC6864499 DOI: 10.1002/cti2.1092

 
Abstract
Objectives. Influenza causes a spectrum of disease from asymptomatic infection to fatal outcome, and pre-existing immunity can alter susceptibility and disease severity. In a household transmission study, we recruited outpatients with confirmed influenza virus infection and prospectively identified secondary infections in their household contacts, therefore identifying infection cases with baseline samples for determining immune-mediated protection from influenza infection.
 
Methods. We examined baseline broadly reactive immune correlates of relevance to universal vaccine development, specifically antibody- dependent cytotoxic (ADCC) antibodies and T-cell responses in functional assays. Antibodies were assessed in a cell-based NK cell degranulation assay by flow cytometry, and T-cell responses were assessed by IFN-c intracellular cytokine staining flow cytometry assay.
 
Results. The magnitude of antibody responses and ADCC function for multiple influenza-specific proteins was lower in participants who became infected, consolidating the role of pre- existing antibodies in protection from seasonal influenza virus infection. Among H1N1-infected contacts, we found that higher levels of pre-existing H1-haemagglutinin ADCC responses correlated with reduced symptom severity. Recent infection boosted the titre and magnitude of haemagglutinin-, neuraminidase- and nucleoprotein-specific ADCC antibodies. Limited T-cell samples precluded conclusions on the role of pre- existing T-cell responses.
 
Conclusions. Overall, ADCC responses are a protective correlate against influenza virus infection that should be considered in future vaccine development and evaluation.Influenza-specific ADCC responses are elevated in uninfected subjects, associated with reduced symptoms and boosted by recent infection, whilst HA stem and NA IgG are also elevated in uninfected participants irrespective of ADCC function.