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

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

doi:10.1186/1479-5876-12-14

Abstract

BackgroundProgressive 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/designAutologous 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.DiscussionTo 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 registrationNCT01824121

Highlights

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
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
Summary of pre-clinical data to support the use of autologous mesenchymal stem cells (MSC) in PSP patients Mesenchymal stem cells (MSC) are multipotent cells that can be isolated from many sources, including bone marrow (BM)

Summary

Discussion

Cell-based advanced therapy is a novel and extremely promising option to cure otherwise untreatable neurodegenerative diseases but there are still several bottle necks that slow the progression and the widening of clinical trials in this context. Intra-arterial infusion resulted again in small ischemic lesions on MR In another open-label clinical trial [65], autologous BM MSCs were transplanted into a sublateral ventricular zone of the brain by stereotaxic surgery in 7 male patients aged 22 to 62 years with advanced PD. In eight patients follow-up MR spectroscopy revealed mean improvements in n-acetylaspartate/creatine ratio These studies demonstrated the feasibility of autologous cell transplantation in patients with parkinsonism, but they did not demonstrate efficacy, because their design did not ensure objective measurements. This technique has been used in the three out of four previous clinical trial in parkinsonisms, with no major adverse events out of the report of asymptomatic microembolism.

Background

Findings

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