Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study

Rosaria Giordano, Margherita Canesi, Maurizio Isalberti, Ioannis Ugo Isaias, Tiziana Montemurro, Mariele Viganò, Elisa Montelatici, Valentina Boldrin, Riccardo Benti, Agostino Cortelezzi, Nicola Fracchiolla, Lorenza Lazzari, Gianni Pezzoli, Rosaria Giordano, Margherita Canesi, Maurizio Isalberti, Ioannis Ugo Isaias, Tiziana Montemurro, Mariele Viganò, Elisa Montelatici, Valentina Boldrin, Riccardo Benti, Agostino Cortelezzi, Nicola Fracchiolla, Lorenza Lazzari, Gianni Pezzoli

Abstract

Background: Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of tauopathies and involves both cortical and subcortical structures. No effective therapy is to date available.

Methods/design: Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors.Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection.

Discussion: To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this "first-in-man" approach and to preliminarily explore its efficacy by excluding the placebo effect.

Trial registration: NCT01824121.

Figures

Figure 1
Figure 1
Pre-clinical data. Bone marrow mesenchymal stem cells from patients affected by progressive supranuclear palsy have the typical spindle-shaped morphology (A), are positive for mesenchymal-specific antigens to an extended flow-cytometric analysis (B) and express BDNF and GDNF as those from healthy subjects, as demonstrated by real time PCR (C) and ELISA (D). BM MSC: bone marrow mesenchymal stem cells; PSP: Progressive Supranuclear Palsy; HS: healthy subjects. The results of flow cytometric analysis, Elisa and PCR are expressed as mean (±SD).
Figure 2
Figure 2
Study design. A) Pilot phase; B) Randomized study.

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