Safety Trial of Stem Cells Completed
Packard scientists evaluated safety of procedure in Phase 1 trial.
Injecting stem cells into the spinal cords of ALS patients appears to be safe.
With only one FDA-approved drug for ALS, scientists and patients alike have held out hope for new interventions, including stem cell therapies. Historically, however, stem cells haven't always translated well from the lab bench to the bedside. Despite their promise in the lab, there have been very few clinical trials of stem cells for ALS in the U.S., and only one using the technique of intraspinal transplantation of stem cells. The results of this Phase I clinical trial, occurring at Emory University in Atlanta, were published in the journals Neurosurgery and Stem Cells. The trial is being conducted by Packard researcher and Emory neuroscientist Jonathan Glass and neurosurgeon Nicholas Boulis, in collaboration with the University of Michigan and Neuralstem, Inc. In these publications the investigators show that fetal neural stem cells injected directly into the spinal cords of ALS patients is a safe procedure.
"This is the first stem cell trial for ALS actually done in the United States," Glass said. "This is also the first trial that has been attempted with neural stem cells, and the first trial with an FDA-monitored approach."
The fate of virtually all cells in the adult body is already set. A liver cell divides to produce another liver cell. An astrocyte begets other astrocytes. In stem cells, however, this future is less certain. A stem cell can differentiate into many different kinds of cells. Neural stem cells, for example, can form the various types of cells found in the nervous system. Given the motor neuron degeneration seen in ALS, scientists had hoped that implantation of stem cells may be an ideal treatment to repair the damage.
No formal clinical trials of stem cells for ALS had been performed in the US, and only a few trials had taken place in Europe. With few precedents to guide them, Glass and colleagues focused intensely on participant safety. No one knew whether patients with ALS could survive such an invasive procedure, or what effect the required immunosuppressant drugs would have on their weakened bodies.
The first trials were performed in patients who were unable to walk, and thus had the least to lose if the surgical procedure caused further damage to the spinal cord. After waiting long enough to ensure that the patients didn't have any serious side effects from the surgery, Glass and colleagues performed bilateral injections of the stem cells--one injection on each side of the lumbar spinal cord. Each injection contained 100,000 neural stem cells. This procedure was made possible with a special injection device developed specifically by Dr. Boulis. From this group, the researchers moved on to two different groups of ambulatory ALS patients, who also received bilateral lumbar injections of stem cells.
As in all Phase I trials, the researchers didn't test whether the stem cell transplants actually helped improve ALS symptoms. The goal of the trial was to assess whether the procedure was safe, which Glass said he and his colleagues accomplished. None of the 12 patients participating in the trial suffered serious complications as a result of the surgery, and seemed to tolerate the immunosuppressant drug regimen well. After the studies were submitted for publication, Glass tested the bilateral injections in five more patients; for this group, the injection site was moved to the cervical spinal cord in the neck. This is a riskier injection site, but also is more likely to benefit the patient. Preliminary data indicates that the cervical injections are also safe.
"We've shown that this procedure is safe, and we can move forward and try and get funding for a Phase II trial where we'll be able to test if it actually works," Glass said.
In future Phase II trials, the researchers intend to increase the number of injections and the number of cells in each injection to establish a therapeutic dosage. The trial will also determine whether the spinal cord stem cell transplants are effective in reversing motor neuron degeneration.
–– Carrie Arnold