Project Details
Projekt
Functional and metabolic investigation of nociceptive mechanisms underlying pain and pain resolution in Bortezomib‐induced polyneuropathy utilizing a patient‐derived in vitro model system
Applicants
Dr. Sabrina Oerter; Professorin Dr. Nurcan Üçeyler
Subject Area
Molecular and Cellular Neurology and Neuropathology
Anaesthesiology
Anaesthesiology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426503586
Peripheral neuropathy and neuropathic pain are common side effects in patients undergoing chemotherapy for cancer. These conditions can substantially influence therapeutic decisions due to their profound impact on patients` health‐related quality of life. The reasons why some patients develop neuropathy and/or neuropathic pain while others do not remain unclear. Additionally, the mechanisms that determine whether pain persists or resolves after treatment cessation are not well understood. Bortezomib (BTZ), a proteasome inhibitor, is the approved first‐line treatment for multiple myeloma patients. Our project aims to elucidate the impact of specific polymorphisms (rs2839629 and rs915854) on the resolution of BTZ‐induced pain (BIPN) and to uncover the underlying neuronal and non‐neuronal mechanisms. To achieve this, we will perform extensive in vitro experiments using advanced 2D mono‐ and co‐culture systems derived from patient‐derived induced pluripotent stem cells (iPSCs). These iPSCs enable the generation of patient‐specific cells of the neural environment, such as sensory‐like neurons and Schwann cells, to model the mechanisms of BIPN and its resolution post‐treatment. We will employ sophisticated techniques such as CRISPR/Cas9 for generating isogenic control cell lines, cellular purification, and functional assays to comprehensively study cellular responses. Additionally, we will conduct transcriptome analysis and advanced electrophysiological assessments using multi‐eletrode array (MEA) analysis and patch‐clamp recordings to identify potential druggable targets for preventing and resolving BIPN, followed by metabolic and functional exploration. Our study combines careful clinical investigation and the collection of human biomaterial from BIPN patients with advanced cellular, molecular, and electrophysiological analysis in fully human and patientderived in vitro cell culture systems. This comprehensive approach furthers our objective to enhance the understanding and treatment of neuropathic pain through state‐of‐the‐art genetic and cellular methodologies.
DFG Programme
Clinical Research Units
