Gastrointestinal (GI) became an independent Disease Area in February 2005. The goal of the GI DA is to carry out innovative research into the pathology of gastrointestinal and other visceral disorders and to identify novel targets for their treatment, as well as providing research support for existing development projects. The initial primary focus as the DA builds up is on functional GI disorders such as irritable bowel syndrome (IBS), dyspepsia and gastro-esophageal reflux disease (GERD), and other visceral conditions with potentially related underlying sensorimotor

dysfunctions, such as overactive bladder. In addition, the GI DA will work closely with the inflammatory bowel disease (IBD) group, currently based within the Autoimmunity & Transplantation DA in Vienna, to identify and develop novel targets for this distressing disease.

Functional GI disorders
Functional gastrointestinal disorders (FGIDs) are chronic or recurrent in nature and classified by symptoms such as visceral pain or discomfort and / or altered bowel habits. Whilst there is no obvious link between an identifiable pathology and the clinical manifestations of FGIDs, disturbances of gastrointestinal motor and sensory function, alterations in the bidirectional communication between the enteric nervous system and the central nervous system as well as psychosocial factors are all implicated in the development of FGIDs. Targeting this neural control network therefore offers numerous opportunities for potential novel therapies affecting motility, hypersensitivity and control of acid reflux. In the western world the prevalence of FGIDs has been estimated to be about 20 % of the population and comprise a major proportion of gastrointestinal and primary care practice. Health-related quality of life is significantly impacted in patients with FGIDs. Zelmac^®/Zelnorm^® is currently the only approved treatment for IBS with constipation and chronic constipation, and there are no true disease modifying agents for the treatment of GERD or dyspepsia.

Overactive bladder
Overactive bladder (OAB) is a chronic and debilitating condition, caused by the untimely contraction of the bladder muscle and resulting in urinary urgency, usually with an increased micturition frequency and nocturia. Micturition is a highly coordinated process involving control of smooth and skeletal muscles of the bladder and urethra, by both the central and peripheral nervous system. Numerous changes have been proposed to underly OAB including alterations in detrusor muscle morphology and innervation, receptor expression, hypersensitivity of urothelial sensory fibres, and changes in central nervous regulation. Although the prevalence increases with age, the problem can affect people of all ages and it is estimated that 20 % of the population over the age of 40 suffers from symptoms of OAB. Antimuscarinics, which directly relax bladder smooth muscle have been the mainstay of drug treatment for OAB, but may be associated with dose-limiting side effects. Modulation of neuronal pathways controlling bladder activity might offer expanded and specific treatment options for OAB with different underlying pathologies.

The Gastrointestinal DA is headed by Alyson Fox and based in Horsham, UK and Basel.

Gremlich HU, Martínez V, Kneuer R, et al. Noninvasive assessment of gastric emptying by near-infrared fluorescence reflectance imaging in mice: pharmacological validation with tegaserod, cisapride, and clonidine. Mol Imaging; 3(4): 303. (2004).

Weber E, Bernhard M, Pfannkuche HJ (2004). The 5-HT4 receptor agonist, tegaserod, stimulates electrolyte/water secretion in the rat colon. Gastroenterology; 126:A147. (2004).

Zelmac®/Zelnorm® (tegaserod)(suspended on March 30)

Enablex®/Emselex® (darifenacine hydrobromide)
This once-daily oral treatment is part of a new group called M3-selective receptor antagonists for overactive bladder.

Zelmac^®/Zelnorm^® for dyspepsia, GERD


DNK333 for IBS with diarrhea