title: Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS.
abstract: 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 × 108cells (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.
  
  
  METHODS
  This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe.
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN. staff.nathan@mayo.edu.
authors: Nathan P
authors: NP
authors: Staff
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Nicolas N
authors: NN
authors: Madigan
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Jonathan
authors: J
authors: Morris
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Mark
authors: M
authors: Jentoft
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Eric J
authors: EJ
authors: Sorenson
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Greg
authors: G
authors: Butler
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Dennis
authors: D
authors: Gastineau
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Allan
authors: A
authors: Dietz
authors: From the Departments of Neurology (N.P.S., N.N.M., E.J.S., A.J.W.), Radiology (J.M.), and Laboratory Medicine and Pathology (M.J., G.B., D.G., A.D.), Mayo Clinic, Rochester, MN.
authors: Anthony J
authors: AJ
authors: Windebank
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000628:therapy*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D059630:Mesenchymal Stem Cells; D008875:Middle Aged; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000000981:diagnostic imaging; D011795:Surveys and Questionnaires; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers