INCOMB

"Combating incontinence, from basic science to clinical practice"

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 Obiettivo del progetto (Objective)

'Incontinence affects almost 66 million people in the European Union. The Over Active Bladder (OAB) symptom complex is one of the major causes for incontinence, with a large number of affected persons and immense associated health care costs. The causes for the over active bladder contractions, underlying the urinary urgency of OAB are unknown, and current treatments are only partially effective. This collaborative and translational project, involving interaction between experimental and clinical urology scientists will focus on OAB and will characterize the different interacting cellular components and signaling systems in the wall of normal urinary bladders and OAB. The release of local mediators in the bladder wall, the properties of a newly described cell type (the interstitial cells, which may play a role in bladder over activity), the sensory signaling pathways (TRPV1-receptors), the receptor interaction and cellular communication are considered in order to create an integrated view on the mechanisms of bladder over activity. A strong emphasis is put on interaction between basic science and clinical applications, using a translational approach involving both specific animal models and human tissue from patients with defined urodynamic information. Several ethical and logistic issues with the use of human tissue are specifically addressed. An important further aspect of the experiments on human tissue is a direct analysis of the links between genetic and the urodynamic data of the patients, using unique biobanks. This will allow us further insight into the mechanisms of disease and possibly to identify new therapeutic targets. In close collaboration with a small company, we will develop an innovative potential physical therapy to affect bladder function. We will develop novel pharmacotherapeutic strategies and diagnostic tools, based on the characterization of cell properties, gene expression, receptors signaling systems of the bladder wall.'

Introduzione (Teaser)

A European project has just completed a comprehensive research programme into Overactive Bladder (OAB) syndrome. Aiming to relieve distressing symptoms for some 66 million Europeans, Incomb researchers have identified several new mechanisms of potential therapeutic value.

Descrizione progetto (Article)

The OAB symptom complex is one of the major causes of incontinence. OAB contractions result in 'urgency'. Not only are the reasons for this phenomenon largely unknown but current treatments are only partially effective or associated with adverse side effects.

The 'Combating incontinence, from basic science to clinical practice' (Incomb) project aimed to establish the pathogenesis of an overactive bladder and improvement of diagnostic tests. For maximum effectiveness, the consortium was made up of experts in lower urinary tract function but with a range of specialisations.

The Incomb team focused on communication between different cell types and developed new techniques to measure signalling components in the bladder lining, sensory nerves, smooth muscle and other cell types. In particular, interstitial cells were identified as particularly interesting as they modulate the contractile activity of the bladder wall. The structure and localisation of interstitial cells was compared in normal and diseased bladders.

Novel receptors were identified on the interstitial cells that could potentially be used for targeted therapy. Transient receptor potential vanilloid (TRPV) 1 receptors were found in different bladder cells and responded to stimulation by heat and acidity. These also offer possibilities for therapy as they are influenced by specific chemical compounds. Considering botulinum toxin as a potential therapy for OAB, the team examined the mechanisms and structural effects of the neurotoxin.

Dissemination has spanned all media outlets. The project has published 60 scientific papers, 39 reviews and 81 conference abstracts. Incomb also organised a major conference in Stockholm and a joint symposium between the EU project TRUST with support from the Swedish Enuresis Academy and the European Association for Urology.

New effective targeted therapies for OAB can significantly improve the quality of life for literally millions of people. Incomb results have also opened up several research corridors for further exploration of this distressing condition.