The involvement of the adaptive immune system plays a significant role in the progression of SPG11 as observed in mouse models, and these responses can be effectively managed through immunomodulation. This project seeks to explore several key questions: 1) Are there active inflammatory processes occurring in the nervous systems of SPG11 patients? 2) What alternative and supplementary approaches exist alongside immunomodulatory therapies? 3) What are the translational implications of our findings for other hereditary spastic paraplegia (HSP) subtypes?

The goal of investigating the translational relevance of neuroinflammation is to identify reliable biomarkers for inflammation within the nervous system and apply this understanding to clinical patient samples. Identifying changes in these biomarkers could offer crucial insights for repurposing established immunomodulatory treatments specifically for SPG11.

Additionally, we will assess whether engaging in physical activity induces immunomodulatory effects in SPG11 and reduces degenerative changes in the nervous systems of our mouse model. The insights gained from this research will also be evaluated in relation to other HSP subtypes and their respective models. Ultimately, this subproject aims to pave the way for new therapeutic strategies that enhance the quality of care for those affected by HSP.