Mosaiques Therapeutics offers various applications for the pharmaceutical industry. The implementation of our CE-MS technology is possible from the very beginning of preclinical development (animal models) to the point of phase III or rather phase IV clinical trials. We are highly experienced in the efficient and time-saving assessment of newly developed as well as already existing pharmaceutical substances. CE-MS profiling will accelerate drug development by ascertainment of statistically significant data from a small number of patients (defined cohorts) plus an enhancement in the determination of pharmaceutical drug safety.
Disease state specific peptide biomarker obtained by our CE-MS technology help to select an appropriate therapy. Therapeutic effects of administered drugs can be displayed and controlled in the developed biomarker model. Furthermore these biomarker can be used to control patient selection, because they are able to detect patients at a pre-progression stage. This enables optimization of applied trial design and therapy (e.g. dosage modification).
Based on preliminary experiments, it is anticipated that toxic effects of drugs will result in indicative changes in the proteome of bodyfluids, before gross pathological changes become apparent. These biomarkers, once validated, will enable a more accurate assessment of potential drug toxicity, consequently identification of potentially serious side effects of therapeutics at an early stage of development and before actual pathological changes.
Together with peptide identification, the technology is an excellent, complimentary, and non-invasive tool to analyze toxicological or other (patho)physiological effects of pharmaceutical compounds.
The development and validation of this platform for rodent urine profiling and biomarker definition will open up new vistas in preclinical research, especially in the definition of therapeutic targets, study design, assessment of drug efficacy, and also safety issues (toxicological studies of drugs or toxins).
Andersen S, Mischak H, Zuerbig P, Parving HH, Rossing P Urinary proteome analysis enables assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria BMC Nephrol. 2010 Nov 1;11:29
Foucher C, Schiffer E, Mischak H, Ansquer JC, Wilbraham D Effect of fenofibrate treatment on the low molecular weight urinary proteome of healthy volunteers Proteomics Clin Appl. 2011 Apr;5(3-4):159-66. doi: 10.1002/prca.201000076
Haubitz M, Good DM, Woywodt A, Haller H, Rupprecht H, Theodorescu D, Dakna M, Coon J, Mischak H Identification and Validation of Urinary Biomarkers for Differential Diagnosis and Evaluation of Therapeutic Intervention in ANCA associated Vasculitis Mol Cell Proteomics 2009 Oct; 8(10):2296-307.
Kistler AD, Siwy J, Breunig F, Jeevaratnam P, Scherl A, Mullen W, Warnock DG, Wanner C, Hughes DA, Mischak H, Wüthrich RP, Serra AL A distinct urinary biomarker pattern characteristic of female Fabry patients that mirrors response to Enzyme Replacement Therapy PLoS One. 2011;6(6):e20534. Epub 2011 Jun 15.
Mischak H, Espandiari P, Sadrieh N, Hanig J Profiling of rat urinary proteomic patterns associated with drug-induced nephrotoxicity using capillary electrophoresis coupled with mass spectrometry as a potential model for detection of drug-induced adverse effects PROTEOMICS - Clinical Applications 2009; 9:1062-1071.
Rouse R, Siwy J, Mullen W, Mischak H, Metzger J, Hanig J Proteomic Candidate Biomarkers of Drug-Induced Nephrotoxicity in the Rat PLoS ONE. 2012;7(4): e34606
Weissinger EM, Metzger J, Dobbelstein C, Wolff D, Schleuning M, Kuzmina Z, Greinix H, Dickinson AM, Mullen W, Kreipe H, Hamwi I, Morgan M, Krons A, Tchebotarenko I, Ihlenburg-Schwarz D, Dammann E, Collin M, Ehrlich S, Diedrich H, Stadler M, Eder M, Holler E, Mischak H, Krauter J, Ganser A. Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host-disease after allogeneic stem cell transplantation. Leukemia. 2013 Jul 11. doi: 10.1038/leu.2013.210.