Contributions
Abstract: P721
Type: Poster
Abstract Category: Therapy - disease modifying - 27 Neuroprotection and Repair
Background: Mesenchymal stem cell-neural progenitors (MSC-NPs) are an autologous bone marrow-derived population of cells with neuroectodermal lineage characteristics currently under investigation as a novel MS treatment targeting CNS repair and regeneration. In mouse EAE, we established that multiple dosing of intrathecal (IT) MSC-NPs was associated with cell migration to lesion areas, suppression of local inflammatory response, trophic support for damaged cells at the lesion site, and improvement in clinical scores of EAE. In a pilot clinical study, IT-MSC-NP treatment also supported the dosing, safety, feasibility, and potential efficacy of this approach in MS.
Objectives: To evaluate safety (phase I) and efficacy (phase II) of repeated dosing of IT-MSC-NP treatment in patients with progressive MS.
Methods: MSCs obtained from bone marrow aspirates were isolated, expanded, and cryopreserved. Prior to dosing, a portion of MSCs were thawed, expanded, and cultured with neural progenitor media to generate MSC-NPs. MSC-NPs were harvested and administered to the patient within 30 minutes. Quality testing of MSC-NPs included sterility, identity, and chromosomal stability. Clinical assessments were performed at baseline, at each treatment, and 3 and 6 months post treatment.
Results: In the 20 patient open-label phase I trial, IT-MSC-NPs were injected at a dose of 10 million cells every 3 months. The only notable adverse events included transient headache and fever found in 72% and 15% of the treatments, respectively. Of the 20 study subjects, 15 (or 75%) demonstrated functional neurological improvement associated with IT-MSC-NP treatment. Improvements were noted in EDSS, 25 foot walk, and muscle strength, and occurred more frequently in ambulatory patients (EDSS ≤ 6.5). In addition, 50% of subjects demonstrated symptomatic and/or urodynamic improvement in bladder function. A phase II trial is underway to investigate efficacy of IT-MSC-NP treatment compared to a placebo sham-IT control. Fifty patients with EDSS between 3.5 and 6.5 will be randomized as matched pairs with a crossover design. The treatment protocol consists of six doses of IT-MSC-NPs spaced two months apart.
Conclusions: IT-MSC-NP therapy is a promising regenerative therapy for progressive MS.
Disclosure: Violaine K Harris: nothing to disclose
James Stark: nothing to disclose
Tamara Vyshkina: nothing to disclose
Valentina Stefanova: nothing to disclose
Saud A. Sadiq: nothing to disclose
Abstract: P721
Type: Poster
Abstract Category: Therapy - disease modifying - 27 Neuroprotection and Repair
Background: Mesenchymal stem cell-neural progenitors (MSC-NPs) are an autologous bone marrow-derived population of cells with neuroectodermal lineage characteristics currently under investigation as a novel MS treatment targeting CNS repair and regeneration. In mouse EAE, we established that multiple dosing of intrathecal (IT) MSC-NPs was associated with cell migration to lesion areas, suppression of local inflammatory response, trophic support for damaged cells at the lesion site, and improvement in clinical scores of EAE. In a pilot clinical study, IT-MSC-NP treatment also supported the dosing, safety, feasibility, and potential efficacy of this approach in MS.
Objectives: To evaluate safety (phase I) and efficacy (phase II) of repeated dosing of IT-MSC-NP treatment in patients with progressive MS.
Methods: MSCs obtained from bone marrow aspirates were isolated, expanded, and cryopreserved. Prior to dosing, a portion of MSCs were thawed, expanded, and cultured with neural progenitor media to generate MSC-NPs. MSC-NPs were harvested and administered to the patient within 30 minutes. Quality testing of MSC-NPs included sterility, identity, and chromosomal stability. Clinical assessments were performed at baseline, at each treatment, and 3 and 6 months post treatment.
Results: In the 20 patient open-label phase I trial, IT-MSC-NPs were injected at a dose of 10 million cells every 3 months. The only notable adverse events included transient headache and fever found in 72% and 15% of the treatments, respectively. Of the 20 study subjects, 15 (or 75%) demonstrated functional neurological improvement associated with IT-MSC-NP treatment. Improvements were noted in EDSS, 25 foot walk, and muscle strength, and occurred more frequently in ambulatory patients (EDSS ≤ 6.5). In addition, 50% of subjects demonstrated symptomatic and/or urodynamic improvement in bladder function. A phase II trial is underway to investigate efficacy of IT-MSC-NP treatment compared to a placebo sham-IT control. Fifty patients with EDSS between 3.5 and 6.5 will be randomized as matched pairs with a crossover design. The treatment protocol consists of six doses of IT-MSC-NPs spaced two months apart.
Conclusions: IT-MSC-NP therapy is a promising regenerative therapy for progressive MS.
Disclosure: Violaine K Harris: nothing to disclose
James Stark: nothing to disclose
Tamara Vyshkina: nothing to disclose
Valentina Stefanova: nothing to disclose
Saud A. Sadiq: nothing to disclose