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P6. GASTROINTESTINAL INFLAMMATION AND MOTILITY
Coordinator:
Dr. J. Panés
Associate Coordinators: Drs. F. Azpiroz and A. Lanas.
The global objective of the Gastrointestinal Inflammation and Motility Programme is to carry out research projects including basic, translational and clinical research aspects, promoting the intra- and inter-group integration of basic and clinical sciences .
In the subprogramme of acid-related diseases, research activities for both environmental and genetic factors linked to increased susceptibility to bleeding in the GI tract in patients taking NSAIDS or antiplatelet agents, as well as research in the treatment and management of H . pylori infection in humans, where substantial contributions have been made possible thanks to the extensive networks of hospitals led by investigators of this area of the CIBEREHD, have been maintained . In addition to these two initiatives, there have been a series of actions aimed at limiting the impact of gastroesophageal reflux disease, to that end actions have commenced to facilitate recognition and apply current therapeutic measures, and on the other hand to limit progression by knowing more about the mechanisms involved and by implementing the diagnostic and therapeutic measures suited to each situation of progression .
The area of Neurogastroenterology and Motility has further developed collaborative studies between the different groups in CIBERehd and with other international teams . On one hand, projects have been developed to characterise the physiopathology of oropharyngeal dysphagia associated with ageing and with neurodegenerative diseases . Three groups of studies have been developed in this area intended to: a) study the expression of TRP family receptors in the human oropharynx and larynx; b) characterise the in vitro pharmacodynamics of different agonists of these receptors, c) evaluation of the in vivo therapeutic effect of different agonists in patients with dysphagia . In this line of work the characterisation of receptors TRPV1, TRPA1 and TRPM8 in samples of human oropharynx and the development of a bioassay with PAC cells expressing these receptors has allowed selecting specific agonists and the development of two clinical studies in patients which have demonstrated that it is possible to improve the oropharyngeal motor response by means of the addition of capsaicin or piperine to the alimentary bolus, opening up the possibility of a completely novel pharmacological treatment of neurogenic and age-related dysphagia . This advancement has also allowed us to conduct studies in which the afferent pathway to the swallowing centre of the brain stem has been stimulated by means of transcutaneous or intrapharyngeal electric stimuli, and we started the study of the mechanisms of cerebral cortex activation by means of multichannel electroencephalography . These studies are performed in the framework of a two-year clinical trial the objective of which is to select the most effective treatment for oropharyngeal dysphagia, having about 50% of patients who have suffered a stroke and thereby preventing serious complications such as malnutrition and aspiration pneumonia .
Research for the development of cell therapies for inflammatory bowel diseases has established the option of an autologous transplant of hematopoietic stem cells as a clinically accepted alternative for the treatment of Crohn’s disease not responding to treatment, which has been recognised in the latest guidelines of the European Bone Marrow Transplant Group . Particularly noteworthy has been the completion of the process of developing another form of cell therapy based on the administration of conditioned autologous tolerogenic dendritic cells obtained from peripheral blood monocytes and the process for the production thereof has been granted a European patent in which CIBEREHD has a considerable participation . Furthermore, has been completed in 2014 the phase 1 study in patients with immunosuppressant- and anti-TNF drug-refractory Crohn’s disease, these results being presented in congresses held throughout 2015 .
Most groups integrated in the program have provided a significant contribution in terms of samples and associated high-quality clinical information for completion of a GWAS in inflammatory bowel diseases . So far, this project has led to the discovery of new susceptibility locus for Crohn’s disease . Particularly
36 CIBEREHD » Annual report 2014