Intraspinal Stem Cell Transplantation in ALS: Results of the First Phase 1 FDA Clinical Trial

Russell N. DeJong Professor of Neurology, University of Michigan
Director, A. Alfred Taubman Medical Research Institute
Director, Program for Neurology Research & Discovery
President, American Neurological Association

Dr. Feldman is on the forefront of applying stem cell research to human disease. Most notably she is the Principal Investigator of the first clinical trial of intraspinal transplantation of stem cells in patients with ALS. To date, 18 of the novel surgeries have been performed with no adverse side effects.
In addition to her clinical practice at the University of Michigan, Dr. Feldman directs a team of 30 scientists in seeking new treatments for neurological diseases including ALS, diabetic neuropathy, Alzheimer’s disease, and muscular dystrophies.  She also is collaborating with Dr. Ben Reubinoff of Hadassah University Medical Center to develop cellular models of ALS using induced pluripotent stem cell (iPS) technology.
She is the author of more than 260 articles, 61 book chapters and 3 books, and is the Principal Investigator of five major National Institutes of Health grants and five clinical trials.

Intraspinal Stem Cell Transplantation in ALS: Results of the first Phase 1 FDA Clinical Trial

The FDA-approved trial, “A Phase 1, Open-label, First-in-human, Feasibility and Safety Study of Human Spinal Cord-derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1,” has been completed in 18 patients with amyotrophic lateral sclerosis (ALS).  Patient cohorts, consisting of 3 ALS patients each, followed a “risk escalation” paradigm progressing from non-ambulatory to ambulatory patients receiving unilateral (n=5) or bilateral (n=10 total) lumbar or cervical injections.  The final cohort of patients that received cervical injections included the same patients that received bilateral lumbar injections.  All injections delivered 100,000 cells in a 10 µl volume, for a dosing range between 500,000 to 1.5 million cells in the various cohorts.  The injection procedure utilized a novel stabilization and injection device that mounts to the patients vertebrae and includes a floating cannula to prevent shearing of the spinal cord during the surgical procedure.  The procedure was well-tolerated by all patients with minimal perioperative or postoperative complications.  Cervical kyphosis developed in one patient following the multi-level laminectomy.  Some patients experienced gastrointestinal distress due to the immunosuppressive paradigm, which included a combination of tacrolimus and mycophenolate.  Although this was a safety trial, clinical progression was monitored and disease progression continued in all patients, with the exception of one patient who exhibited remarkable clinical and electrophysiological improvements.  Presently, 4 patient deaths have occurred and postmortem analyses are underway.  Results of this trial demonstrate that intraspinal transplantation of neural progenitor cells in patients with ALS is feasible and well-tolerated.  The established safety of this approach supports future trial phases examining therapeutic efficacy of neural stem cell transplantation for this yet untreatable, devastating neurodegenerative disorder.