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Tnf-alpha-binding protein-imprinted polymers for treating crohn's disease

The mission of the consortium is to utilize state-of-the-art pharmaceutical approaches and develop tnf-alpha-binding protein-imprinted polymers for the specific elimination of tnf-alpha from the gastrointestinal tract hence improving the therapy of currently untreatable crohn's disease.

Crohn’s Disease (CD) is a serious inflammatory bowel disease (IBD) affecting a large numbers of patients worldwide (its global prevalence is between 0.3 cases and 16.5 cases per 100,000) and representing a major health concern. CD tends to present initially in the teens and twenties, with another peak incidence in the fifties to seventies, although the disease can occur at any age. There is no known pharmaceutical or surgical cure for CD. Treatment options are restricted to controlling symptoms, maintaining remission, and preventing relapse. In cases where remission is possible, relapse can be prevented and symptoms controlled with medication, lifestyle and dietary changes, changes to eating habits, reduction of stress, moderate activity and exercise. Surgery is generally counter-indicated and has not been shown to prevent remission. Until recently, the management of CD consisted of the stepwise use of mesalazine, corticosteroids and immunomodulators. Anti-tumor necrosis factor (TNF) agents are recent additions to the CD-treatment algorithm. It is known that the cytokine, tumor necrosis factor-alpha (TNF-a), plays a central role in the pathogenesis of CD. One of the therapeutic approaches developed for CD patients is a TNF-a-binding antibody, infliximab (Remicade©), which has demonstrated remission in one third of the CD patients studied. Infliximab is administered intravenously and has numerous adverse effects. Patients treated with infliximab are at increased risk for developing serious infections along with lymphoma and other malignancies. TNF-a is a multifunctional proinflammatory cytokine essential to the immune system, but has many anti-tumor properties, and has been studied in a variety of cancer therapies including sarcoma, melanoma, renal cell and pancreatic carcinoma. Therefore there is a real concern for an increased risk of both hematologic and solid cancers with the systemic administration of TNF-a inhibitors. Given its well established role in inducing inflammation in the gastrointestinal (GI) tract along with its systemic anti-carcinogenic effects, it would be important to develop gut slective anti-TNF-a agents against CD that lack the adverse effects of systemically administered TNF inhibitors. These non-absorbable anti-TNF agents could be administered orally to bind TNF-a specifically and inhibit its effects locally in the GI tract. To address these challenges, a consortium has been formed by leading experts for the development of novel TNF-inhibiting agents against CD. The consortium possesses state-of-the-art technologies for the inhibition of TNF-a. By utilizing its proprietary molecularly imprinted polymers (MIP) technology, Semorex Ltd. has recently developed a unique approach for synthesizing selective non-absorbable protein-binding polymers. These protein-imprinted polymers (PIPs) possess antibody-like selectivity along with high stability, allowing applications where antibodies cannot be used, such as passage through the highly acidic environment of the stomach and through the GI tract. By specifically binding TNF-a in the GI tract, anti-TNF PIPs would reduce influence of TNF-a on bowel inflammation and development of CD. For testing various anti-inflammatory strategies including TNF-interference, researchers of Pharmacoidea Ltd. have been developing in vitro reporter gene assays of NF-kappaB, a TNF-a inducible proinflammatory transcription factor, and have hands-on knowledge in the pharmaceutical validation of drug candidates in various in vivo GI inflammatory models such as CD. The consortium's strategy is to bring together talented Israelis and Hungarians committed and capable of the innovation required for the betterment of CD therapy. The research team is selected from forward thinking biologists, chemists and medical doctors interested in solving important medical problems and translating scientific results rapidly into innovative therapeutics by rational drug discovery and chemical engineering. With state-of-the art bioinformatics, molecular biology and pharmacology tools, researchers of the consortium will screen and assess the bioactivity of PIPs for the inhibition of TNF-a, a cytokine with a major role in CD. The consortium has the scientific methodologies that can validate efficacy of the anti-TNF-a PIPs using in vitro and in vivo models of CD. Employing bioinformatics IT-tools, the state of the art of knowledge will be recorded and associated with the relevant studies. All available experimental data and pertinent information from in house experiments, scientific literature data, and patents will be curated and assembled into a dossier structured similar to a standard Investigational New Drug (IND) application document. Moreover, the assembled dossier will store state of the art proprietary information about the Chemistry, Manufacturing and Control (CMC).
Acronym: 
PIP-4-CD
Project ID: 
9 605
Start date: 
01-03-2015
Project Duration: 
24months
Project costs: 
500 000.00€
Technological Area: 
Micro- and Nanotechnology related to Biological sciences
Market Area: 
Therapeutic

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