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Combination of personalised therapies


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After spinal cord injury a variety of different mechanisms exacerbate the pathology, including propagation of inflammatory response, cell loss and the formation of a glial scar. In order to simultaneously target different aspects of the pathology, Stefano Pluchino and collaborators at the University of Cambridge explore autologous brain stem cells and RNAi-based nanodrugs for people with traumatic spinal cord injuries.

The right combination
RNA-based nanotherapeutics have shown great promise in cancer research. However, this study is their first application in an in vivo experimental model of spinal cord injury. This promising technology was used to diminish the expression of a specific pro-inflammatory protein, lipocalin 2, during the acute phase of the injury. The aim was to create a more favorable environment for the transplantation of directly induced neural stem cells (iNSCs). This particular type of NSCs, having so far seen limited study in spinal cord injury, possesses many practical and ethical advantages for potential for future clinical translation of cell therapy.

The results
Pre-treatment with anti-lipocalin 2 RNA nanotherapeutics prior to iNSC transplantation led to functional recovery accompanied by a reduction of glial scarring and amelioration of the inflammatory response.
This study addresses an interesting facet of therapeutic techniques employed in spinal cord injury: targeting different aspects of the pathology by combining multiple technologies holds the potential to promote synergistic effects and stronger therapeutic outcomes.

This study was published in Molecular Therapy and was supported by Wings for Life.

Source: Alice Braga, Sara Bandiera, Jeroen Verheyen, Regan Hamel, Carola Rutigliani, Frank Edenhofer, Jayden Aaron Smith and Stefano Pluchino. Combination of In Situ Lcn2 pRNA-RNAi Nanotherapeutics and iNSC Transplantation Ameliorates Experimental SCI in Mice.  Mol Ther. 2020;S1525-0016(20)30411-1. doi:10.1016/j.ymthe.2020.08.001.

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