Project Details
Projekt
Promoting humeral head fracture healing by local immunomodulation - A phase I/IIa, prospective, mono-centre, randomized, open labelled, controlled study (P16)
Subject Area
Medical Informatics and Medical Bioinformatics
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 427826188
Based on previous pre-clinical work within the Research Unit 2165, Winkler and Geißler will use a first-in-men clinical phase I/IIa study to unravel the details of immune-modulation: Promoting humeral head fracture healing by local immunomodulation in a prospective, mono-centre, randomised, open labelled, controlled study, the prostacyclin analogue Iloprost will be used to locally dampen CD8+ effector T cell activity and simultaneously increase CD4+ regulatory T cell levels via the modulation of the cyclic AMP/protein kinase A (cAMP/PKA) pathway. Local Iloprost administration in a mouse osteotomy model resulted in reduced CD8+ T cell levels and reduced pro-inflammatory cytokine secretion at the site of injury and significantly improved bone healing. Shaping the local inflammatory response is a suitable and safe approach to improve human bone regeneration especially in elderly patients with an experienced immune system. In a prospective, randomised phase I/IIa study safety and efficacy of a local Iloprost administration will be assessed in patients suffering from proximal humeral head fractures which have a high non-union rate. Winkler and Geißler also aim to characterise the patients’ immune experience to gain a more mechanistic understanding of how the bone repair process is altered by local cAMP/PKA pathway modulation and to determine the direct or indirect effects of the immunomodulation on bone tissue and its function.
DFG Programme
Collaborative Research Centres
Applicant Institution
shared FU Berlin and HU Berlin through:
Charité - Universitätsmedizin Berlin
Charité - Universitätsmedizin Berlin
Project Heads
Dr. Sven Geißler; Professor Dr. Tobias Winkler
