Current Issue

Volume 20, Number 4, Jan-Mar(Winter) 2019, Serial Number: 80 Pages: 592-598

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, M.D, 1, #, Leila Arab, M.D, 2, #, Neda Jarooghi, M.Sc, 1, Tina Bolurieh, M.Sc, 1, Fatemeh Abbasi, M.Sc., 1, Soura Mardpour, Ph.D., 1, Vajihe Azimyian, Ph.D., 1, Fatemeh Moeininia, M.D., 1, Saman Maroufizadeh, M.Sc., 3, Leila Sanjari, M.D., 4, Seyedeh Esmat Hosseini, M.Sc., 5, Nasser Aghdami, M.D., Ph.D., 1, *,
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Medicine, ACECR, Tehran, Iran
Intensive Care Unit, Mostafa Khomeini Hospital, Tehran, Iran
Student Research Committee, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
*Corresponding Address: P.O.Box: 16635-148 Department of Regenerative Medicine Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran Email:Nasser.aghdami@royaninstitute.org

*The first two authors equally contributed to this work.

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).