Safety, Feasibility of Intravenous and Intrathecal Injection of Autologous Bone Marrow Derived Mesenchymal Stromal Cells in Patients with Amyotrophic Lateral Sclerosis: An Open Label Phase I Clinical Trial

Seyed Massood Nabavi, Leila Arab, Neda Jarooghi, Tina Bolurieh, Fatemeh Abbasi, Soura Mardpour, Vajihe Azimyian, Fatemeh Moeininia, Saman Maroufizadeh, Leila Sanjari, Seyedeh Esmat Hosseini, Nasser Aghdami, Seyed Massood Nabavi, Leila Arab, Neda Jarooghi, Tina Bolurieh, Fatemeh Abbasi, Soura Mardpour, Vajihe Azimyian, Fatemeh Moeininia, Saman Maroufizadeh, Leila Sanjari, Seyedeh Esmat Hosseini, Nasser Aghdami

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) is the most severe disorder within the spectrum of motor neuron diseases (MND) that has no effective treatment and a progressively fatal outcome. We have conducted two clinical trials to assess the safety and feasibility of intravenous (IV) and intrathecal (IT) injections of bone marrow derived mesenchymal stromal cells (BM-MSCs) in patients with ALS.

Materials and methods: This is an interventional/experimental study. We enrolled 14 patients that met the following inclusion criteria: definitive diagnosis of sporadic ALS, ALS Functional Rating Scale (ALS-FRS) ≥24, and ≥40% predicted forced vital capacity (FVC). All patients underwent bone marrow (BM) aspiration to obtain an adequate sample for cell isolation and culture. Patients in group 1 (n=6) received an IV and patients in group 2 (n=8) received an IT injection of the cell suspension. All patients in both groups were followed at 24 hours and 2, 4, 6, and 12 months after the injection with ALS-FRS, FVC, laboratory tests, check list of side effects and brain/spinal cord magnetic resonance imaging (MRI). In each group, one patient was lost to follow up one month after cell injection and one patient from IV group died due to severe respiratory insufficiency and infection.

Results: During the follow up there were no reports of adverse events in terms of clinical and laboratory assessments. In MRI, there was not any new abnormal finding. The ALS-FRS score and FVC percentage significantly reduced in all patients from both groups.

Conclusion: This study has shown that IV and IT transplantation of BM-derived stromal cells is safe and feasible (Registration numbers: NCT01759797 and NCT01771640).

Keywords: Amyotrophic Lateral Sclerosis; Bone Marrow; Intrathecal; Intravenous; Mesenchymal Stromal Cell.

Conflict of interest statement

There is no conflict of interest in this study.

Copyright© by Royan Institute. All rights reserved.

Figures

Fig.1
Fig.1
Study flow diagram.
Fig.2
Fig.2
Expressions of bone marrow derived mesenchymal stromal cell (BM-MSC) surface markers.
Fig.3
Fig.3
The trend of amyotrophic lateral sclerosis-functional rating scale (ALS-FRS) and forced vital capacity during 12 month follow up in patients of both group. A. ALS-FRS and B. Forced vital capacity (FVC) in the intravenous (IV) and intrathecal (IT) groups due to worsening of patients’ conditions. ALS-FRS and FVC data are mean ± SEM.

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