Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS
Autor: | Anthony J. Windebank, Allan B. Dietz, Eric J. Sorenson, Nathan P. Staff, Greg W. Butler, Mark E. Jentoft, Jonathan M. Morris, Dennis A. Gastineau, Nicolas N. Madigan |
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Rok vydání: | 2016 |
Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Stromal cell Nerve root Urology Mesenchymal Stem Cell Transplantation Severity of Illness Index Transplantation Autologous Article 03 medical and health sciences 0302 clinical medicine Surveys and Questionnaires Severity of illness Adipocytes Humans Medicine Amyotrophic lateral sclerosis Injections Spinal Aged business.industry Amyotrophic Lateral Sclerosis Mesenchymal stem cell Brain Mesenchymal Stem Cells Middle Aged medicine.disease Magnetic Resonance Imaging Transplantation Clinical trial Treatment Outcome 030104 developmental biology Spinal Cord Female Neurology (clinical) business Biomarkers 030217 neurology & neurosurgery Lumbosacral joint Follow-Up Studies |
Zdroj: | Neurology. 87:2230-2234 |
ISSN: | 1526-632X 0028-3878 |
Popis: | Objective:To determine the safety of intrathecal autologous adipose-derived mesenchymal stromal cell treatment for amyotrophic lateral sclerosis (ALS).Methods:Participants with ALS were enrolled and treated in this phase I dose-escalation safety trial, ranging from 1 × 107 (single dose) to 1 × 108 cells (2 monthly doses). After intrathecal treatments, participants underwent standardized follow-up, which included clinical examinations, revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, blood and CSF sampling, and MRI of the neuroaxis.Results:Twenty-seven patients with ALS were enrolled and treated in this study. The safety profile was positive, with the most common side effects reported being temporary low back and radicular leg pain at the highest dose level. These clinical findings were associated with elevated CSF protein and nucleated cells with MRI of thickened lumbosacral nerve roots. Autopsies from 4 treated patients did not show evidence of tumor formation. Longitudinal ALSFRS-R questionnaires confirmed continued progression of disease in all treated patients.Conclusions:Intrathecal treatment of autologous adipose-derived mesenchymal stromal cells appears safe at the tested doses in ALS. These results warrant further exploration of efficacy in phase II trials.Classification of evidence:This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe. |
Databáze: | OpenAIRE |
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