Successful SPG4 diagnosis without genetic test

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.

Dr Sardina

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.

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