Abstract
Background. Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Objective. To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas. Data Sources and Review Methods. A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Results. Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM. Conclusions and Implications for Practice. Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E52-E63 |
| Journal | Otolaryngology - Head and Neck Surgery (United States) |
| Volume | 148 |
| Issue number | 4 SUPPL. |
| DOIs | |
| State | Published - Apr 2013 |
Bibliographical note
Funding Information:Competing interests: Lauren O. Bakaletz obtained sponsored research funding from GlaxoSmithKline Biologicals, Inc. J. Christopher Post is on the Scientific Advisory Board for Otonomy.
Funding Information:
Recently, novel OM genes in chemical (ENU) mutagenesis programs linked to phenotypic screens for deafness and vestibular signs were discovered. The gene targeting and the international efforts, including the European Mouse Disease Clinic (EUMODIC), Knockout Mouse Project (KOMP), and North American Conditional Mouse Mutagenesis (NORCOM) programs, to produce KO of all genes in the mouse genome are gaining momentum. In addition, embryonic stem cells are a publicly available resource for the scientific community. The International Mouse Phenotyping Consortium (IMPC) is funded by the National Institutes of Health (NIH), MRC Wellcome Trust, and Genome Canada. The 3 consortia—UC Davis–Toronto, Regeneron-Jax, and Baylor–Sanger Wellcome Trust–MRC Harwell—are funded to share the work. Phase 1 (2011-2016) aims to turn 5000 targeted embryonic stem cells into mutant mice and also perform the baseline phenotyping (includes ABRs). Studies at Sanger Wellcome Trust indicate that this effort will lead to the identification of novel sensorineural and OM mutants. Phase 2 (2016-2021) of the program will aim to deliver an additional 15,000 mutants.
Keywords
- Biochemistry
- Cell signaling
- Chemokine
- Cytokine
- Inflammation
- Innate immunity
- Molecular biology
- Otitis media
- Tissue remodeling