Safety of Autologous MSC Infusion to Treat Epilepsy

Summary

• The goal of this study was to evaluate the safety and efficacy of autologous MSC application for the therapy of drug-resistant symptomatic epilepsy. Adult (18-60 years old) patients (pts) of both sexes suffering from refractory epilepsy with frequent (\>5 events per month) seizures were included in this study. The pts were randomized to the standard treatment with anti-epileptic drugs (control group, 30 pts) or anti-epileptic drugs plus autologous mesenchymal stem cells (MSCs) (study group, 30 pts). The pts in the study group received one intravenous injection of ex vivo expanded MSCs (40-101 x 106 cells) and one subsequent endolumbal injection of neuroinduced MSCs (2.7 - 8.0 x 106 cells). Both the unfavorable reactions to MSC infusions and the clinical effects, including complications, were examined. The unfavorable reactions to the MSC injections included local pain or hemorrhage at the site of injection and systemic reactions of the central nervous system (CNS; i.e., hyperthermia, fatigue, and myalgia).The possible beneficial effects of therapy in the two groups of pts were examined based on clinical observations and electroencephalography measurements (prior and 12 months after the application of the MSC-based therapy). To determine potential changes in disease progression, the signs of cognitive impairment, behavioral disorders, and particularly, changes in seizure character and frequency were evaluated using the National Hospital Scale of Seizure Severity. The main points of disease monitoring were "yes" or "no" responses (to therapy), seizure frequency (per month), and remission of disease. Electroencephalography (EEG) recordings were performed to evaluate electrical alpha, beta, theta and delta waves based on standard and additional criteria. The paroxismality index, the peak frequency of EEG activity, the index of slow activity, and the summarized points of EEG pathology signs were calculated for each patient. All assessments were performed for the pts in the control and study groups, and the obtained data were compared to identify the potential differences between the two pts groups. Therapy was terminated when immediate unfavorable reactions to the MSC injections were observed. The final observation of each patient included clinical and EEG assessments at the time point of 12 months (or more) after the application of the MSC-based therapy.

Timeline

Start

2011-04

Primary completion

2017-12

Completion

2019-12

Publications

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• Background Shakhbazau AV, Goncharova NV, Kosmacheva SM, Kartel' NA, Potapnev MP. Plasticity of human mesenchymal stem cell phenotype and expression profile under neurogenic conditions. Bull Exp Biol Med. 2009 Apr;147(4):513-6. doi: 10.1007/s10517-009-0547-6. English, Russian.
• Hlebokazov F, Dakukina T, Potapnev M, Kosmacheva S, Moroz L, Misiuk N, Golubeva T, Slobina E, Krasko O, Shakhbazau A, Hlavinski I, Goncharova N. Clinical benefits of single vs repeated courses of mesenchymal stem cell therapy in epilepsy patients. Clin Neurol Neurosurg. 2021 Aug;207:106736. doi: 10.1016/j.clineuro.2021.106736. Epub 2021 Jun 8.
• Hlebokazov F, Dakukina T, Ihnatsenko S, Kosmacheva S, Potapnev M, Shakhbazau A, Goncharova N, Makhrov M, Korolevich P, Misyuk N, Dakukina V, Shamruk I, Slobina E, Marchuk S. Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Adv Med Sci. 2017 Sep;62(2):273-279. doi: 10.1016/j.advms.2016.12.004. Epub 2017 May 10.

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