03. January 2019
Preview: Catalogue Editorial 2019
Transglutaminases in Translation
Driven by clinical programs, the transglutaminase researcher community enters an exciting and promising year. Sponsored by Dr. Falk Pharma, our tissue transglutaminase (TG2)-blocker ZED1227* entered a phase 2a proof-of-concept study for the treatment of celiac disease in mid 2018. The study aims to eventually enroll 160 patients in 20 centers all over Europe. The results of the “study on the efficacy and tolerability of a 6-week treatment with ZED1227 capsules vs. placebo in subjects with well-controlled celiac disease undergoing gluten challenge” are expected in 2019.
Targeting TG2 for the treatment of fibrotic disorders has been discussed for several years. In this regard, an anti-human tissue transglutaminase monoclonal antibody (UCB7858, “Zampilimab”) is under development. In late 2018, UCB Biopharma got approval for a phase 1/2 study “to evaluate safety/tolerability, pharmacokinetics, and efficacy of UCB7858 in adult kidney transplant recipients with chronic allograft injury” in Spain.
We are confident that, based on the outcome of such clinical trials, the transglutaminase community will profit. We anticipate that obtaining substantial data by means of target validation will increase the overall awareness of the importance of the transglutaminase field to pharmaceutical companies and to government funding agencies - resulting in more projects and increased financial support.
We would like to mention Zedira’s own research that refocuses on TG2. The 2nd
generation of reversible inhibitors* has been optimized for systemic indications (e.g. fibrotic disorders), providing complementary small molecules to the monoclonal antibody approach.
A current trend in oncology and, indeed in some other areas of clinical research, is the development of antibody drug conjugates (ADCs). Such innovative biomolecules enable the targeted delivery of cytotoxic payloads to cancer cells. Enzymatic conjugation by microbial transglutaminase (MTG) is a state-of-the-art method for the production of site specifically conjugated and homogeneous ADCs with a defined drug-to-antibody ratio.
Our highly purified MTG is the product of choice for this purpose and we expect to meet the increasing requirements/demands of our customers for this enzyme, both in quantity and in conformity with stringent regulatory requirements.
Autoantibodies to TG2 (celiac disease) and TG3 (dermatitis herpetiformis) are well established biomarkers. In this context, Zedira continues to produce high quality diagnostic antigens. Moreover, our patent protected anti-TG6-ab-ELISAs permit the detection of autoantibodies to TG6, a novel biomarker in gluten ataxia.
Factor XIII activity measurement is a diagnostic tool not only in FXIII-deficiency, but also for coagulation in routine blood tests. Our precise fluorogenic FXIII-activity assay (A101, F001) is currently adapted to a fully automated coagulation analyzer.
Finally, these and many more aspects of “Transglutaminases in Translation” will be highlighted in a special issue of Analytical Biochemistry, to be launched in early 2020: “Transglutaminases in Translation – Novel Tools and Methods Impacting on Diagnostics and Therapeutics”.
It is our pleasure to be guest editors for this special issue, and we welcome all of you in the transglutaminase field to consider submitting relevant manuscripts.
On behalf of the entire Zedira team
Ralf Pasternack and Martin Hils