Imaging-based method a potential biomarker
SPG4 HSP has been successfully differentiated from other HSP types, and from healthy cells, without genetic test, by a single physical measure using imaging of PBMCs, a type of blood cell.
The method also detects the effects of changes in spastin protein levels, thus making this a potential biomarker of effectiveness of candidate drug treatments.
This study builds on previous findings by Dr Gautam Wali who developed a method to identify SPG4 without genetic test in 2021 using skin cell samples.
Background and purpose: Microtubule defects are a common feature in several neurodegenerative disorders, including hereditary spastic paraplegia. The most frequent form of hereditary spastic paraplegia is caused by mutations in the SPG4/SPAST gene, encoding the microtubule severing enzyme spastin. To date, there is no effective therapy available but spastin-enhancing therapeutic approaches are emerging; thus prognostic and predictive biomarkers are urgently required.
Methods: An automated, simple, fast and non-invasive cell imaging-based method was developed to quantify microtubule cytoskeleton organization changes in lymphoblastoid cells and peripheral blood mononuclear cells.
Results: It was observed that lymphoblastoid cells and peripheral blood mononuclear cells from individuals affected by SPG4-hereditary spastic paraplegia show a polarized microtubule cytoskeleton organization. In a pilot study on freshly isolated peripheral blood mononuclear cells, our method discriminates SPG4-hereditary spastic paraplegia from healthy donors and other hereditary spastic paraplegia subtypes. In addition, it is shown that our method can detect the effects of spastin protein level changes.
Conclusions: These findings open the possibility of a rapid, non-invasive, inexpensive test useful to recognize SPG4-hereditary spastic paraplegia subtype and evaluate the effects of spastin-enhancing drug in non-neuronal cells.
SOURCE: Eur J Neurol. 2023 Jun;30(6):1734-1744. doi: 10.1111/ene.15756. Epub 2023 Mar 26. PMID: 36815539 © 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
New cellular imaging-based method to distinguish the SPG4 subtype of hereditary spastic paraplegia
Francesca Sardina 1 , Davide Valente 1 2 , Gaia Fattorini 1 3 , Ettore Cioffi 4 , Gianmarco Dalla Zanna 4 , Alessandra Tessa 5 , Daniela Trisciuoglio 1 , Silvia Soddu 2 , Filippo M Santorelli 5 , Carlo Casali 4 , Cinzia Rinaldo 1
1. Institute of Molecular Biology and Pathology (IBPM), Consiglio Nazionale delle Ricerche (CNR), c/o Sapienza University of Rome, Rome, Italy.
2. Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
3. Department of Biology and Biotechnology, “Charles Darwin” Sapienza University of Rome, Rome, Italy.
4. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
5. Molecular Medicine, IRCCS Fondazione Stella Maris, Pisa, Italy.