Jonathan Glass, professor of neurology at Emory University in School of Medicine, is the principal investigator of a phase 2 clinical trial that examined the safety of intraspinal injection of human spinal cord–derived neural stem cells in people with amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.
This clinical trial was not designed to determine whether the treatment was effective, which is odd given that the trial was a phase 2 trial. Glass and his collaborators noted that the transplanted stem cells did not slow down the progression of the disease. However, given that the trial was not designed to detect efficacy, it is difficult to draw any hard-and-fast conclusions.
ALS is a disorder in which the motor neurons of the brain and spinal cord degenerate. Motor neuron degeneration causes progressive loss of muscle control, which includes breathing and swallowing (leading to death). There are no treatments that can stop ALS.
“Though there were two serious complications related to the treatment, the level of acceptable risk for treating patients with ALS, where the prognosis is poor and treatments are limited, is arguably higher than that for more benign disorders,” said Dr. Glass.
In this study, 15 ALS patients who manifested their first signs and symptoms of the disease within two years of the start of the study, were treated at three different university hospitals.
The participants were divided into five treatment groups that received increasing doses of stem cells. This trial was an “open-label” trial, which means that the participants knew they were getting active stem cell treatments.
Participants received bilateral (both sides) injections into the cervical spinal cord between the C3 and C5 regions. The final group received injections into both the lumbar (L2-L4) and cervical cord through two separate surgical procedures.
The numbers of injections ranged from 10 to 40, and the number of cells injected ranged from two million to 16 million. Because of the large range of injections and stem cells injected, determining the safety of these treatments was probably more important that the efficacy of the treatments.
During the nine months of follow-up, patients were assessed for side effects from the intraspinal injections and progression of the disease, according to the functional rating scale. Most of the side effects were related to temporary pain associated with surgery and to medications that suppress the immune system.
Two people developed serious complications related to the treatment. One patient developed spinal cord swelling that caused pain, sensory loss and partial paralysis, and another patient developed central pain syndrome; a neurological condition caused by damage to or dysfunction of the central nervous system (CNS), which includes the brain, brainstem, and spinal cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or Parkinson’s disease.
The participants’ functioning was compared to three historical control groups, and there was no difference in how fast the disease progressed between those
who received stem cells and those who did not. This is a significant finding because injecting cells into the spinal cord might actually accelerate the progression of the disease. However, this study seemed to show that 10-40 injections into the spinal do not affect the progression of ALS.
However, Glass cautioned that no conclusions can be draw about effectiveness of the treatment from such a small, non-blinded, non-placebo-controlled study.
“This study was not designed, nor was it large enough, to determine the effectiveness of slowing or stopping the progression of ALS. The importance of this study is that it will allow us to move forward to a larger trial specifically designed to test whether transplantation of human stem cells into the spinal cord will be a positive treatment for patients with ALS,” Dr. Glass said.
These results were published in Jonathan D. Glass et al., “Transplantation of spinal cord–derived neural stem cells for ALS: Analysis of phase 1 and 2 trials,” Neurology, June 2016 DOI:10.1212/WNL.0000000000002889.