BACKGROUND: No United States-based clinical trials have attempted delivery of biological therapies directly to the spinal cord for treatment of amyotrophic lateral sclerosis (ALS) because of the lack of a meaningful US Food and Drug Administration-authorized cell candidate and a validated delivery approach. OBJECTIVE: To assess safety of delivery of a neural stem cell-based treatment into the upper lumbar segments of the ALS spinal cord in the first US Food and Drug Administration-authorized phase I trial. METHODS: Each microinjection series comprised 5 injections (10 μL/injection) separated by 4 mm. Each injection deposited 100,000 neural stem cells derived from a fetal spinal cord. Twelve patients were treated with either unilateral or bilateral injections. Group A, nonambulatory patients, underwent unilateral (n = 3) or bilateral (n = 3) lumbar microinjections. Groups B and C were ambulatory (n = 3 each) and, respectively, received unilateral or bilateral injections. Patients are followed clinically and radiologically to assess potential toxicity of the procedure. RESULTS: Twelve patients have received a transplant. There was one instance of transient intraoperative somatosensory-evoked potentials depression. In the immediate postoperative period, there was 1 episode of urinary retention requiring Foley catheter reinsertion. By discharge, none had a documented motor function decrement. Two patients required readmission and reoperation for cerebrospinal fluid leak or suprafascial wound dehiscence (n = 1 each). Two deaths occurred at 8 and 13 months postsurgery; neither was related to the surgical transplant. CONCLUSION: Our experience in 12 patients supports the procedural safety of unilateral and bilateral intraspinal lumbar microinjection. Completion of this phase I safety trial is planned by proceeding to cervical and combined cervical + lumbar microinjections in ALS patients.
BACKGROUND: No United States-based clinical trials have attempted delivery of biological therapies directly to the spinal cord for treatment of amyotrophic lateral sclerosis (ALS) because of the lack of a meaningful US Food and Drug Administration-authorized cell candidate and a validated delivery approach. OBJECTIVE: To assess safety of delivery of a neural stem cell-based treatment into the upper lumbar segments of the ALS spinal cord in the first US Food and Drug Administration-authorized phase I trial. METHODS: Each microinjection series comprised 5 injections (10 μL/injection) separated by 4 mm. Each injection deposited 100,000 neural stem cells derived from a fetal spinal cord. Twelve patients were treated with either unilateral or bilateral injections. Group A, nonambulatory patients, underwent unilateral (n = 3) or bilateral (n = 3) lumbar microinjections. Groups B and C were ambulatory (n = 3 each) and, respectively, received unilateral or bilateral injections. Patients are followed clinically and radiologically to assess potential toxicity of the procedure. RESULTS: Twelve patients have received a transplant. There was one instance of transient intraoperative somatosensory-evoked potentials depression. In the immediate postoperative period, there was 1 episode of urinary retention requiring Foley catheter reinsertion. By discharge, none had a documented motor function decrement. Two patients required readmission and reoperation for cerebrospinal fluid leak or suprafascial wound dehiscence (n = 1 each). Two deaths occurred at 8 and 13 months postsurgery; neither was related to the surgical transplant. CONCLUSION: Our experience in 12 patients supports the procedural safety of unilateral and bilateral intraspinal lumbar microinjection. Completion of this phase I safety trial is planned by proceeding to cervical and combined cervical + lumbar microinjections in ALSpatients.
Authors: Jonathan D Glass; Vicki S Hertzberg; Nicholas M Boulis; Jonathan Riley; Thais Federici; Meraida Polak; Jane Bordeau; Christina Fournier; Karl Johe; Tom Hazel; Merit Cudkowicz; Nazem Atassi; Lawrence F Borges; Seward B Rutkove; Jayna Duell; Parag G Patil; Stephen A Goutman; Eva L Feldman Journal: Neurology Date: 2016-06-29 Impact factor: 9.910
Authors: Chester H Ho; Ronald J Triolo; Anastasia L Elias; Kevin L Kilgore; Anthony F DiMarco; Kath Bogie; Albert H Vette; Musa L Audu; Rudi Kobetic; Sarah R Chang; K Ming Chan; Sean Dukelow; Dennis J Bourbeau; Steven W Brose; Kenneth J Gustafson; Zelma H T Kiss; Vivian K Mushahwar Journal: Phys Med Rehabil Clin N Am Date: 2014-08 Impact factor: 1.784
Authors: Thais Federici; Carl V Hurtig; Kentrell L Burks; Jonathan P Riley; Vibhor Krishna; Brandon A Miller; Eric A Sribnick; Joseph H Miller; Natalia Grin; Jason J Lamanna; Nicholas M Boulis Journal: J Vis Exp Date: 2012-12-07 Impact factor: 1.355