Inhibition of dysregulated tissue transglutaminase (tTG, TG2)

Celiac disease is the most common chronic inflammation of the small intestine affecting more than 1% of the Western population. For decades it has been known that the external trigger is gluten (a cereal protein) inducing the inflammation in genetically susceptible people. Gluten – or more precisely the gliadin peptides derived by digestion – fits perfectly to the active site of tissue transglutaminase. In the small intestinal mucosa, gliadin peptides are enzymatically modified by tissue transglutaminase (also known as TG2).
This modification, a deamidation in a chemical sense, results in the introduction of a negative charge into the gliadin molecule by transforming glutamine to glutamic acid. Subsequently the deamidated gliadin is recognized by the immune cells triggering and amplifying the inflammation process. The vicious circle consisting of inflammation, transglutaminase secretion and activation, deamidation of gliadin and further stimulation of the immune response destroys the villi responsible for absorption of nutrition.

Zedira’s therapeutic approach is intercepting the vicious circle by blocking dysregulated tissue transglutaminase. To achieve this, we developed drug candidate ZED1227, a small molecule representing a novel class of transglutaminase inhibitors. ZED1227 is a peptidomimetic compound obtained by rational drug design. ZED1227 combines high potency and selectivity for the target tissue transglutaminase.

ZED1227 has been licensed to Dr. Falk Pharma (Freiburg, Germany) for preclinical and clinical development, approval and marketing in Europe.
Following successful preclincal, pharmaceutical and clinical phase 1 (single ascending dose and multiple ascending dose) development, ZED1227 entered Phase 2a clinical trials in celiac disease patients in spring 2018.

Until a drug is approved by the authorities, a strict gluten free diet (cumbersome but efficient) is the only way for patients and their families to handle celiac disease. In addition to physicians, national patients’ organizations provide excellent support for managing the disease.

Products

  • Zedira offers a huge portfolio of reliable specialist transglutaminase related products meant to catalyze research and development, both in academia and industry.

News  

  • Press release: Dr. Falk Pharma and Zedira announce start of the phase 2a proof of concept study of ZED1227 for the treatment of celiac disease
  • Artikel in DLG-Lebensmittel – 06/2017 zur Bestimmung von Transglutaminase in Lebensmitteln (deutsch)
  • Zedira publication: Microbial Transglutaminase Used in Bread Preparation at Standard Bakery Concentrations Does Not Increase Immunodetectable Amounts of Deamidated Gliadin
  • Pressemitteilung: Dr. Falk Pharma und Zedira geben den Abschluss der Phase 1b-Studie für ZED1227 zur Zöliakie-Therapie bekannt und planen Start der Wirksamkeitsstudie
  • Press release: Dr. Falk Pharma and Zedira announce completion of phase 1b clinical trial of ZED1227 for the treatment of celiac disease and move on to proof of concept study
  • Press Release: Dr. Falk Pharma GmbH and Zedira enter a phase 1b clinical trial for a celiac disease drug
  • Zedira publication: Microbial transglutaminase has a lower deamidation preference than human tissue transglutaminase on a celiac disease relevant wheat gliadin T-cell epitope
  • Press release: Additional subsidy funding for clinical development of a celiac disease drug
  • Pressemitteilung: Zusätzliche Fördermittel für die klinische Entwicklung eines Zöliakie-Medikamentes
  • Press Release: Cooperation between Zedira and Cardiff University - Transglutaminase 6 is the focus of new research into ataxia
  • Press Release: Dr. Falk Pharma and Zedira enter phase I clinical trials for a celiac disease drug
  • Press release: Zedira receives further funding to develop Factor XIIIa-blockers for safe anticoagulation

Blog  

Events  

  • Life Sciences 2019: Post-translational modifications and cell signalling

    17.03.2019 - 18.03.2019
    Nottingham, UK

  • 10th International meeting of the Society for research on the Cerebellum and Ataxias (SRCA)

    16.05.2019 - 17.05.2019
    Sheffield, UK

  • 18th International Celiac Disease Symposium ICDS

    04.09.2019 - 07.09.2019
    Paris, France