Analysis of phase 1 and 2 trials testing the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers.
Links to some earlier articles:
- First U.S. stem cells transplanted into spinal cord | CNN.com (January 2010)
- Stem cell treatment goes from lab to operating room | CNN.com (May 2010)
Transplantation of spinal cord–derived neural stem cells for ALS
Analysis of phase 1 and 2 trials
Authors: Jonathan D. Glass, MD; Vicki S. Hertzberg, PhD; Nicholas M. Boulis, MD; Jonathan Riley, MD; Thais Federici, PhD; Meraida Polak, RN; Jane Bordeau, RN; Christina Fournier, MD; Karl Johe, PhD; Tom Hazel, PhD; Merit Cudkowicz, MD; Nazem Atassi, MD; Lawrence F. Borges, MD; Seward B. Rutkove, MD; Jayna Duell, RN; Parag G. Patil, MD; Stephen A. Goutman, MD; Eva L. Feldman, MD, PhD
Objective: To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers.
Methods: This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5). The final group received injections into both the lumbar (L2-L4) and cervical cord through 2 separate surgical procedures. Participants were assessed for adverse events and progression of disease, as measured by the ALS Functional Rating Scale–Revised, forced vital capacity, and quantitative measures of strength. Statistical analysis focused on the slopes of decline of these phase 2 trial participants alone or in combination with the phase 1 participants (previously reported), comparing these groups to 3 separate historical control groups.
Results: Adverse events were mostly related to transient pain associated with surgery and to side effects of immunosuppressant medications. There was one incident of acute postoperative deterioration in neurologic function and another incident of a central pain syndrome. We could not discern differences in surgical outcomes between surgeons. Comparisons of the slopes of decline with the 3 separate historical control groups showed no differences in mean rates of progression.
Conclusions: Intraspinal transplantation of human spinal cord–derived neural stem cells can be safely accomplished at high doses, including successive lumbar and cervical procedures. The procedure can be expanded safely to multiple surgical centers.
Classification of evidence: This study provides Class IV evidence that for patients with ALS, spinal cord transplantation of human stem cells can be safely accomplished and does not accelerate the progression of the disease. This study lacks the precision to exclude important benefit or safety issues.