ANN ARBOR, Mich. — A patient with amyotrophic lateral sclerosis (ALS) received six million stem cells injected to the spinal cord in a procedure Jan. 8 at the University of Michigan Health System – the 25th time an ALS patient has undergone the experimental injections as part of a national clinical trial.
The 66-year-old man has returned home and will receive follow-up monitoring and testing to help U-M neurologists assess the safety and any potential effect of the injections. He is the 7th patient to undergo the surgery in Phase 2 of the trial, which began in September and follows a 15-patient Phase 1 trial that produced no adverse side effects in patients undergoing the surgery.
Eva L. Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the U-M Medical School and director of the A. Alfred Taubman Medical Research Institute, is the principal investigator for the trial. Feldman has led the analysis of results from the Phase 1 trial which concluded in 2012.
In Phase 1, three of the 15 patients received a second injection of stem cells, for a total of 18 surgeries in that segment of the trial. The seven surgeries so far in Phase 2 bring the total number to 25.
“We’re pleased that as we reach this important milestone, none of our patients in either phase of the trial have experienced any adverse side effects as a result of the stem cell implantation,” said Feldman. “We are very excited to note that escalating the number of stem cells per patient does not appear to increase that risk.”
In data presented in 2013, spinal cord injections of between 500,000 to 1.5 million cells were delivered safely and tolerated well in a Phase 1 trial conducted at Emory. The researchers reported possible signs that in one subgroup of participants who received the highest dose of stem cells, ALS progression may have been interrupted.
Additional patients with the condition, also known as Lou Gehrig’s disease, are being evaluated for possible participation in the trial at U-M and Emory University. Patients in the Phase 2 trial will receive up to 16 million of the specially engineered stem cells.
The Phase II trial is approved by the U.S. Food and Drug Administration and funded by Neuralstem, Inc., the Maryland-based company whose stem-cell product the trial is testing. It seeks to study any effect that injected stem cells might have on motor neurons – muscle-controlling nerve cells that die in ALS patients, eventually robbing them of the ability to walk, speak and breathe.
Parag Patil, M.D., Ph.D., a U-M neurosurgeon and biomedical engineer, performed the four operations that have been completed at U-M. In each case, the patient’s spinal column was unroofed and the spinal cord exposed to receive the cells. The cells are introduced via a custom-designed delivery device that is affixed to the subject’s spinal bones so that it moves with the patient’s breathing throughout the process.
Patil, an assistant professor in U-M’s departments of Neurosurgery, Neurology, Biomedical Engineering and Anesthesiology, and a Young Friends of the Taubman Institute Emerging Scholar, also serves as a paid engineering consultant to Neuralstem to further develop the cell-delivery device.
This Phase 2 dose escalation trial is designed to treat up to 15 ambulatory patients in five different dosing cohorts, under an accelerated dosing and treatment schedule.
The first 12 patients, divided into four cohorts, will receive injections only in the cervical region of the spinal cord, where breathing function is controlled. The first cohort of three patients received 10 cervical region injections of 200,000 cells per injection. The second cohort of three patients received 20 cervical region injections of 200,000 cells per injection. The trial has now progressed to the third cohort of three patients receiving 20 cervical injections of 300,000 cells per injection. If this proves safe, the fourth cohort will receive 400,000 stem cells per injection with 20 cervical injections.
The last three Phase 2 patients will receive injections in both the cervical and the lumbar spinal regions. These patients will receive 20 injections of 400,000 cells each in the lumbar region in addition to the 20 injections they will already have received in their cervical region.
The trial also accelerates the treatment schedule, and is designed to progress at the rate of one cohort per month with one month observation periods between cohorts. Researchers expect all of the patients could be treated by the end of the second quarter in 2014.
Patients seeking information on the trial should contact the relevant center. For the University of Michigan Health System, please visit: http://www.umclinicalstudies.org/HUM00072488. For Emory Healthcare, please call (404) 778-7777.
For more information on ALS treatment and research at the U-M Health System, visit http://umhealth.me/UM-ALS .