Translational drug discovery and development with the use of tissue‐relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy
| Autor: | Paul J. Bryce, Danping Ding-Pfennigdorff, Matthias Herrmann, Klaus Flechsenhar, Frank O. Nestle, Peter Florian, Eckart Bartnik |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Skin Absorption Dermatology Bioinformatics Biochemistry Dermatitis Atopic 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Drug Development In vivo Psoriasis Drug Discovery Ustekinumab medicine Animals Humans Molecular Biology Skin Drug discovery business.industry Atopic dermatitis medicine.disease Dupilumab Disease Models Animal 030104 developmental biology Drug development Secukinumab Dermatologic Agents business Biomarkers medicine.drug |
| Zdroj: | Experimental Dermatology. 29:4-14 |
| ISSN: | 1600-0625 0906-6705 |
| DOI: | 10.1111/exd.13942 |
| Popis: | Due to the clinical development of drugs such as secukinumab, ustekinumab and dupilumab, major changes have been achieved in the treatment of patients diagnosed with psoriasis and atopic dermatitis. In academia and the pharmaceutical industry, research is increasingly moving towards the development of bispecific antibodies and multi-specific nanobodies, as there is a compelling need for new treatment modalities for patients suffering from autoimmune or malignant disease. The purpose of this review is to discuss aspects of translational drug development with a particular emphasis on indications such as psoriasis and atopic dermatitis. The identification of biomarkers, the assessment of target organ pharmacokinetic and pharmacodynamics interactions and a wide range of in vitro, ex vivo and in vivo models should contribute to an appropriate prediction of a biological effect in the clinical setting. As human biology may not be perfectly reflected by approaches such as skin equivalents or animal models, novel approaches such as the use of human skin and dermal microperfusion assays in healthy volunteers and patients appear both reasonable and mandatory. These models may indeed generate highly translationally relevant data that have the potential to reduce the failure rate of drugs currently undergoing clinical development. |
| Databáze: | OpenAIRE |
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