Safety and Effectiveness of Cell Therapy in Neurodegenerative Diseases: Take-Home Messages From a Pilot Feasibility Phase I Study of Progressive Supranuclear Palsy

Rosaria Giordano, Margherita Canesi, Maurizio Isalberti, Giovanni Marfia, Rolando Campanella, Daniele Vincenti, Viviana Cereda, Alessandra Ranghetti, Chiara Palmisano, Ioannis Ugo Isaias, Riccardo Benti, Giorgio Marotta, Lorenza Lazzari, Tiziana Montemurro, Mariele Viganò, Silvia Budelli, Elisa Montelatici, Cristiana Lavazza, Araceli Rivera-Ordaz, Gianni Pezzoli, Rosaria Giordano, Margherita Canesi, Maurizio Isalberti, Giovanni Marfia, Rolando Campanella, Daniele Vincenti, Viviana Cereda, Alessandra Ranghetti, Chiara Palmisano, Ioannis Ugo Isaias, Riccardo Benti, Giorgio Marotta, Lorenza Lazzari, Tiziana Montemurro, Mariele Viganò, Silvia Budelli, Elisa Montelatici, Cristiana Lavazza, Araceli Rivera-Ordaz, Gianni Pezzoli

Abstract

Mesenchymal stromal cells (MSCs) are multipotent cells with anti-inflammatory properties. Here we tested the safety of MSCs in patients with progressive supranuclear palsy (PSP; ClinicalTrials.gov: NCT01824121; Eudract No. 2011-004051-39). Seven patients were treated. To improve the safety, protocol adjustments were made during the performance of the study. The objectives of our work were: (1) to assess the safety of MSCs and (2) to identify critical issues in cell therapies for neurodegenerative diseases. Autologous MSCs from the bone marrow of PSP patients were administered through the internal carotid arteries. 1-year survival and number of severe adverse events were considered as safety endpoints. Clinical rating scales, neuropsychological assessments, gait and posture analysis, single-photon emission computed tomography, positron emission tomography, and brain magnetic resonance (BMR) were performed at different follow-up times. Peripheral blood levels of inflammatory cytokines were measured before and after cell infusion. Six of the seven treated patients were living 1 year after cell infusion. Asymptomatic spotty lesions were observed at BMR after 24 h in six of the seven treated patients. The last patient in the preliminary cohort (Case 5) exhibited transiently symptomatic BMR ischemic alterations. No severe adverse events were recorded in the last two treated patients. Interleukin-8 serum concentrations decreased in three patients (Case 2, 3, and 4). An adaptive study design, appropriate and up-to-date efficacy measures, adequate sample size estimation, and, possibly, the use of a cellular and/or allogeneic cell sources may help in performing phase II trials in the field.

Keywords: Parkinson’s disease; cell therapy; mesenchymal stromal cells (MSCs); posture; progressive supranuclear palsy (PSP).

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Giordano, Canesi, Isalberti, Marfia, Campanella, Vincenti, Cereda, Ranghetti, Palmisano, Isaias, Benti, Marotta, Lazzari, Montemurro, Viganò, Budelli, Montelatici, Lavazza, Rivera-Ordaz and Pezzoli.

Figures

FIGURE 1
FIGURE 1
Study flow diagram showing the patient enrollment, allocation, follow-up, and analysis in the phase I study. IMP, investigational medicinal product; MSCs, mesenchymal stromal cells.
FIGURE 2
FIGURE 2
Clinical assessments data per single patient and at each time point. (A) UPDRS III (Unified Parkinson’s Disease Rating Scale part III, motor score); (B) PSP – RS (PSP Rating Scale). The star symbol (*) identifies those measures that overcome the stabilization threshold as defined in the text.

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Source: PubMed

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