Frank Edenhofer and Sébastien Couillard-Després, Leopold-Franzens-University, Innsbruck, Austria

Combinatorial approach to preserve and restore neuronal circuits

Funded in: 2021, 2022, 2023

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Problem: A therapy critically depends on the development of combinatorial treatments
Target: Combination of two innovative pre-clinical technologies
Goal: Groundwork for future SCI treatment

Further progress in the field of traumatic spinal cord injury (tSCI) therapy critically depends on the development of combinatorial treatments targeting both the acute and the chronic phase. To achieve this, an Austrian collaboration will explore a novel clinical strategy based on the combination of two innovative pre-clinical technologies:

  1. treatment with extracellular vesicles (EV) at the acute phase to reduce inflammation and scar formation
  2. transplantation of induced neural stem cells (iNSCs) during the chronic phase to restore neuronal connectivity and hopefully improve long-term motor and sensory functions

A major objective in the advancement of regenerative therapies for SCI is the restoration of neuronal connectivity. Stem cells of the nervous system would represent an ideal source for cell replacement. However, the access to appropriate cells from adult patients is limited. By employing patient-specific iNSCs, the neuroscientists will make use of a novel, safe and autologous cellular source for transplantation in the chronic phase.

The researchers will explore a stepwise therapeutic strategy employing a rat model for tSCI. In step one, they will repeatedly apply EVs close to the lesion site directly after the injury and thereafter into the blood stream for seven days post injury. By this, the scientists expect to reduce scar formation and create a more hospitable lesion environment for subsequent cellular treatment. In step two, they will graft human iNSCs into the lesion site 30 days post-injury. To find out about the synergistic effects of both treatments, they will continuously monitor functional ameliorations in behavioral testings for up to six months after transplantation.

By analyzing the marker expression as well as genome-wide transcriptomic profiles of the graft they will get deep insights into the fate of engrafted iNSCs and the putatively formed regenerative microenvironment. This project will lay the groundwork for future SCI treatment for patients affected by chronic SCI.