PDE8 in Inflammatory Bowel Disease
Participants:
The
National Hospital of the Faroe Islands
Background
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.
Contact:
Referenced Publications:
(1) http://www.epicom-ecco.eu/start.dll/EXEC
(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.
