Mesenchymal stem cell application in children with subacute sclerosing panencephalitis

Abstract

Subacute sclerosing panencephalitis (SSPE) is a serious, often fatal disease that responds poorly to current treatment modalities. Recently, the ability of mesenchymal stem cells (MSCs) to produce neurotrophic factors and inflammatory molecules has placed them among potential treatment agents for neurological conditions. We report the results of four patients treated with MSC for SSPE. The patients were followed up clinically, and by periodical laboratory evaluations, magnetic resonance imaging (MRI), and electroencephalography. One patient deteriorated to stage III of the disease, two patients remained in the same stage, and one died from disease progression and respiratory problems. Neurological findings and electroencephalography scores were consistent with the clinical course of the patient whereas MRI showed new inflammatory lesions in two patients. This is the first report of the application of MSC in SSPE. No benefit is demonstrated.

Subacute sclerosing panencephalitis

“…Ribavirin, in SSPE, has been used with either intrathecal or intraventricular route (40 to 60 mg/kg/day), frequently, in combination with interferon‐α and isoprinosine . In a report, four patients of SSPE were treated with mesenchymal stem cells, but in all patients, no benefit was demonstrated …”

Myelin disorders and stem cells: as therapies and models

“…MS is a demyelinating disorder with a significant inflammatory component (Compston and Coles, 2008; ALD Cells: Allogenic umbilical cord blood or hematopoietic stem cells Transplantation: Intravenous injection with slight variations among centers n = 94 patients from 43 centers (Peters et al, 2004) -Low rate of severe complications -86% engraftment of donor cells -Increased survival of early stage patients -Not recommended for late stage patients Method: Retrospective analysis comparing data of Peters et al (2004) with data from nontransplanted patients n = 94 transplanted 283 nontransplanted patients (Mahmood et al, 2007) -Increased survival rate of ccALD patients (especially early-stage patients) -Not recommended for patients at advanced stages or without cerebral involvement Cells: Allogenic hematopoietic stem cells Transplantation: Intravenous injection n = 60 patients (Miller et al, 2011) -No severe complications -Increased survival of patients who received early in disease -Benefit to neurological function Cells: ABCD1 gene corrected autologous hematopoietic stem cells Transplantation: Intravenous infusion after complete myeloablation n = 2 patients (Cartier et al, 2009) -Functional ABCD1 was introduced into HSCs using lentivirus -Longitudinally, 10%-15% of transplanted HSCs expressed ABCD1 (ALD) protein -Decreased demyelination -Neurological benefits similar to HSC transplantation -Decreased plasma VLCFA levels SSPE Cells: Autologous mesenchymal stem cells Transplantation: Intrathecal and intravenous injection n = 5 patients (Kuskonmaz et al, 2015) -1 death before the evaluation -1 death from disease progression -1 deteriorated to stage III -2 remained stable Constantinescu et al, 2011). Myelin loss disrupts the ability of the nervous system to efficiently communicate, resulting in physical, mental, and psychiatric problems (Compston and Coles, 2008).…”

“…The distinct processes leading to infection of cells in the brain are poorly understood and no cure for SSPE exists (Schneider-Schaulies et al, 2003;Anlar and Yalaz, 2011). As MSCs have been used in ALD with positive outcomes and in MS for their immunomodulatory characteristics, Kuskonmaz et al (2015) transplanted five SSPE patients with autologous bone marrow-derived MSCs. One patient died of respiratory problems prior to evaluation and none of the remaining four patients showed any improvements ( Table 2).…”

Stem cells and their potential therapeutic use in subacute sclerosing panencephalitis

“…In this issue, physicians from Turkey (a country where SSPE is rampant) describe the first clinical trial of MSCs for the treatment of SSPE . Five children with clinically worsening SSPE received autologous infusions of MSCs.…”

“…In this issue, physicians from Turkey (a country where SSPE is rampant) describe the first clinical trial of MSCs for the treatment of SSPE. 5 Five children with clinically worsening SSPE received autologous infusions of MSCs. The cells were administered recurrently via intravenous and intrathecal routes, and the children were monitored clinically, radiographically, and by laboratory studies.…”