A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome
BACKGROUNDSevere forms of idiopathic nephrotic syndrome (INS) require prolonged immunosuppressive therapies and repeated courses of high-dose glucocorticoids. Mesenchymal stromal cells (MSCs) have promising immunomodulatory properties that may be employed therapeutically to reduce patient exposure to medications and their side effects.METHODSWe performed a phase I open-label trial assessing safety and feasibility of autologous bone marrow-derived MSCs (BM-MSCs) in children and young adults with severe forms of steroid-dependent nephrotic syndrome. Following autologous BM-MSC preparation and infusion, oral immunosuppression was tapered. Safety, efficacy, and immunomodulatory effects in vivo were monitored for 12 months.RESULTSSixteen patients (10 children, 6 adults) were treated. Adverse events were limited and not related to BM-MSC infusions. All patients relapsed during follow-up, but in the 10 treated children, time to first relapse was delayed (P = 0.02) and number of relapses was reduced (P = 0.002) after BM-MSC infusion, compared with the previous 12 months. Cumulative prednisone dose was also reduced at 12 months compared with baseline (P < 0.05). No treatment benefit was observed in adults.In children, despite tapering of immunosuppression, clinical benefit was mirrored by a significant reduction in total CD19+, mature, and memory B cells and an increase in regulatory T cells in vivo up to 3-6 months following BM-MSC infusionCONCLUSIONTreatment with autologous BM-MSCs is feasible and safely reduces relapses and immunosuppression at 12 months in children with severe steroid-dependent INS. Immunomodulatory studies suggest that repeating MSC infusions at 3-6 months may sustain benefit.TRIAL REGISTRATIONEudraCT 2016-004804-77.FUNDINGAIFA Ricerca Indipendente 2016-02364623.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
JCI insight - 8(2023), 18 vom: 22. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vivarelli, Marina [VerfasserIn] |
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| Links: |
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| Themen: |
Clinical Trial, Phase I |
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| Anmerkungen: |
Date Completed 25.09.2023 Date Revised 11.10.2023 published: Electronic EudraCT: 2016-004804-77 Citation Status MEDLINE |
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| doi: |
10.1172/jci.insight.169424 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360611761 |
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| 245 | 1 | 2 | |a A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUNDSevere forms of idiopathic nephrotic syndrome (INS) require prolonged immunosuppressive therapies and repeated courses of high-dose glucocorticoids. Mesenchymal stromal cells (MSCs) have promising immunomodulatory properties that may be employed therapeutically to reduce patient exposure to medications and their side effects.METHODSWe performed a phase I open-label trial assessing safety and feasibility of autologous bone marrow-derived MSCs (BM-MSCs) in children and young adults with severe forms of steroid-dependent nephrotic syndrome. Following autologous BM-MSC preparation and infusion, oral immunosuppression was tapered. Safety, efficacy, and immunomodulatory effects in vivo were monitored for 12 months.RESULTSSixteen patients (10 children, 6 adults) were treated. Adverse events were limited and not related to BM-MSC infusions. All patients relapsed during follow-up, but in the 10 treated children, time to first relapse was delayed (P = 0.02) and number of relapses was reduced (P = 0.002) after BM-MSC infusion, compared with the previous 12 months. Cumulative prednisone dose was also reduced at 12 months compared with baseline (P < 0.05). No treatment benefit was observed in adults.In children, despite tapering of immunosuppression, clinical benefit was mirrored by a significant reduction in total CD19+, mature, and memory B cells and an increase in regulatory T cells in vivo up to 3-6 months following BM-MSC infusionCONCLUSIONTreatment with autologous BM-MSCs is feasible and safely reduces relapses and immunosuppression at 12 months in children with severe steroid-dependent INS. Immunomodulatory studies suggest that repeating MSC infusions at 3-6 months may sustain benefit.TRIAL REGISTRATIONEudraCT 2016-004804-77.FUNDINGAIFA Ricerca Indipendente 2016-02364623 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
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| 650 | 4 | |a Nephrology | |
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| 700 | 1 | |a Algeri, Mattia |e verfasserin |4 aut | |
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| 700 | 1 | |a Emma, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a L'Erario, Ines |e verfasserin |4 aut | |
| 700 | 1 | |a Busutti, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Rota, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Capelli, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Introna, Martino |e verfasserin |4 aut | |
| 700 | 1 | |a Todeschini, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Casiraghi, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Perna, Annalisa |e verfasserin |4 aut | |
| 700 | 1 | |a Peracchi, Tobia |e verfasserin |4 aut | |
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| 700 | 1 | |a Ruggenenti, Piero |e verfasserin |4 aut | |
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