Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, rand
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Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study Rosaria Giordano1*, Margherita Canesi2, Maurizio Isalberti3, Ioannis Ugo Isaias2,4, Tiziana Montemurro1, Mariele Viganò1, Elisa Montelatici1, Valentina Boldrin1, Riccardo Benti5, Agostino Cortelezzi6, Nicola Fracchiolla6, Lorenza Lazzari1 and Gianni Pezzoli2
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 Keywords: Progressive supranuclear palsy, Parkinson’s disease, Mesenchymal stem and stromal cells, Advanced therapy medicinal products, Cellular therapy
Background Progressive supranuclear palsy (PSP) is a rare form of parkinsonism with a prevalence of about 0.5 cases per 100,000 inhabitants and with an incidence of 5.3 new cases every 100,000 inhabitants [1,2]. Its etiology is unknown. From a pathological point of view, the disease consists in a neurodegenerative process that involves the basal ganglia, the brainstem, the prefrontal cortex and the cerebellum, with accumulation of a tau protein - hence * Correspondence: [email protected] 1 Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy Full list of author information is available at the end of the article
the classification as tauopathy [3]. Onset typically occurs after 40 years of age. The symptoms include bradykinesia, proximal and axial rigidity and early postural instability. The key sign, which gives the disease its name, is the supranuclear paralysis of vertical gaze, followed by abnormalities of horizontal gaze. This sign usually appears t
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