Clinical benefits of single vs repeated courses of mesenchymal stem cell therapy in epilepsy patients

Gene and Cell Therapy for Epilepsy: A Mini Review

“…Cell therapy for epilepsy includes a variety of approaches, including the use of MSCs ( Abdanipour et al, 2011 ; Mohammed et al, 2014 ; Park et al, 2015 ; Hlebokazov et al, 2017 , 2021 ; Fukumura et al, 2018 ; Salem et al, 2018 ; Melin et al, 2019 ; Szczepanik et al, 2020 ; Wang et al, 2021 ), mononuclear cells ( Costa-Ferro et al, 2010 ; Leal et al, 2014 ; DaCosta et al, 2018 ), cells of the nervous system ( Baraban et al, 2009 ; Waldau et al, 2010 ; Cunningham et al, 2014 ; de Gois da Silva et al, 2018 ; Upadhya et al, 2019 ), and encapsulated cells expressing various therapeutic factors ( Kanter-Schlifke et al, 2009 ; Kuramoto et al, 2011 ; Nikitidou et al, 2014 ; Falcicchia et al, 2018 ; Paolone et al, 2019 ), as well as exosomes ( Long et al, 2017 ; Xian et al, 2019 ). Cell therapy is an alternative treatment that can be used to reduce the incidence rate of seizures in epilepsy, including drug-resistant epilepsy, as shown in several clinical studies ( Hlebokazov et al, 2017 , 2021 ; DaCosta et al, 2018 ; Milczarek et al, 2018 ; Szczepanik et al, 2020 ).…”

“…Numerous studies have shown that the administration of undifferentiated MSCs can significantly decrease the frequency of seizures ( Hlebokazov et al, 2017 , 2021 ; Milczarek et al, 2018 ; Szczepanik et al, 2020 ), improve cognitive ( Fukumura et al, 2018 ; Milczarek et al, 2018 ; Wang et al, 2021 ) and motor functions ( Mohammed et al, 2014 ), increase the number of neurons ( Abdanipour et al, 2011 ), reduce oxidative stress ( Salem et al, 2018 ). The introduction of MSCs promotes the survival of GABAergic interneurons ( Mohammed et al, 2014 ; Fukumura et al, 2018 ).…”

“…For example, phase I/II clinical trials have demonstrated that the administration of antiepileptic drugs along with one or two intravenous and intrathecal administrations of MSCs has been safe and effective in treating patients with drug-resistant epilepsy. Combined use of levetiracetam (an antiepileptic drug) and MSCs led to a decrease in the frequency of seizures, and a repeated course of MSC administration contributed to a further improvement in the patients’ condition (NCT02497443) ( Hlebokazov et al, 2017 , 2021 ).…”

Mesenchymal stem cell therapy for focal epilepsy: A systematic review of preclinical models and clinical studies

“…Of the 18 publications, 15 met the inclusion criteria and were included in this article. [21][22][23][26][27][28][29][30][31][32][33][34][35][36][37] From the included 15 publications, 11 were preclinical models (Table 1) and 4 were clinical studies (one case report and three phase 1 clinical trials; Table 2).…”

“…In addition, Park et al (2015) evaluated the metabolic activity of the hippocampus through PET scanning and demonstrated increased glucose metabolism in animals treated with MSCs. Because novel therapeutic studies involving treatment with MSCs for epilepsy are scarce and in the early stages of development, [34][35][36][37] our literature search yielded only four phase 1 clinical studies, [34][35][36][37] one as a case report 34 ; all of the reports had the primary objective of feasibility and safety with a secondary objective to evaluate efficacy. [34][35][36][37] In addition, all four studies included a follow-up period of at least 1 year to provide support for their objective to measure efficacy.…”