PDE8 in Inflammatory Bowel Disease.
The incidence of Inflammatory Bowel Disease (IBD) on the Faroe Islands is more than double what is found throughout the rest of Scandinavia and Europe and therefore, represents a pressing public health need (1). Recent epidemiological studies with the Faroese IBD cohort demonstrate that the current high rates of IBD on the Faroe Islands reflect an increase in incidence over the past 15-20 years (2).
Mouse models of inflammation have suggested that pharmacological inhibition of Phosphodiesterase 8A (PDE8A), a cytosolic enzyme, effects signaling pathways implicated in the pathogenesis of IBD and other autoimmune diseases (3). In humans, AKAP13-PDE8A fusion transcripts have been shown to be highly recurrent in colorectal cancer biopsies.
The study of PDE control of IBD inflammation is clinically important and conceptually relevant and may lead to the detection of previously unrecognized biomarkers of autoimmunity and new therapeutics (4).
Main Goal: Establish if Phosphodiesterase (PDE) 8A is a potential therapeutic target for Inflammatory Bowel Disease (IBD).
This goal will be addressed to determining the expression pattern of PDE8A mRNA (by in situ hybridization) and protein (by immunohistochemistry) in biopsies from individuals with Ulcerative Colitis or Crohn´s Disease. Completion of this study will represent the first clinical data in an ongoing effort to develop highly specific therapies based on targeting PDE8A to treat IBD and other autoimmune diseases.
The National Hospital of the Faroe Islands
(2) Nielsen KR, Jacobsen S, Olsen K, Jess T, Gaini S. Incidence and clinical characteristics of inflammatory bowel disease in the Faroe Islands during 2005–2009. 2013.
(3) Vang AG, Ben-Sasson SZ, Dong H, et al. PDE8 regulates rapid Teff cell adhesion and proliferation independent of ICER. PloS One. 2010
(4) Nome,T, Thomassen G, Bruun J, et al.Common Fusion Transcripts Identified in Colorectal Cancer Cell Lines by High-Throughput RNA Sequencing. Translational Oncology. 2013.
Amanda Vang, Ph.D.