NEW ORLEANS—Bilateral injections of stem cells into the spine are safe and may slow disability progression in patients with amyotrophic lateral sclerosis (ALS), according to research presented at the 2013 Annual Meeting of the American Neurological Association.
Stem cell DNA appears to be present in the spine after transplantation even when the patient has not had immunosuppression for more than 216 days. Transplantation early in the course of the disease may be less risky for patients in whom ALS does not affect the bulbar region, said Eva Feldman, MD, PhD.
Dr. Feldman, Professor of Neurology at the University of Michigan in Ann Arbor; Jonathan Glass, MD, Professor of Neurology and Pathology at Emory University; and Nicholas Boulis, MD, Assistant Professor of Neurosurgery at Emory University, recently completed the first human phase I trial of a stem cell transplantation procedure developed to provide neuroprotection or neural replacement in patients with ALS. After a complete laminectomy and visualization of the spinal cord and determination of the appropriate locations for transplantation, the clinician injects stem cells using a specially developed cannula that matches the size of the patient’s spinal cord. Injections are 4 mm apart and may be administered unilaterally or bilaterally to the lumbar or cervical areas.
Dr. Feldman and colleagues studied 15 patients with ALS in a risk-escalation trial of the surgical procedure. For each patient, an MRI guided the appropriate location of the transplantation. The first three patients were not ambulatory and had unilateral transplantation into the lumbar spine. They received five injections of 100,000 stem cells each. After the investigators observed evidence of the procedure’s safety, they performed bilateral lumbar injections for three additional nonambulatory patients. Each patient received 10 injections.
After establishing the safety of transplantation in nonambulatory patients, the researchers performed unilateral lumbar transplantation on three ambulatory patients, followed by bilateral lumbar transplantation on three ambulatory patients. Ascertainment of safety in these subjects enabled the investigators to perform unilateral cervical transplantation in three patients. Five injections in areas C3 through C5 for each patient were administered. A final cohort of three ambulatory patients who had received bilateral lumbar transplantation then received unilateral cervical transplantation.
No serious adverse events were associated with the surgery. The six nonambulatory patients received transplantation in 2010, and two of those patients were alive in October 2013. Transplantation did not appear to affect disease progression in those patients, and the two remaining living patients have chosen to be intubated.
Of the three ambulatory patients with unilateral lumbar transplantation, two fared well at more than 800 days after surgery. One of the three patients had ALS that affected the bulbar region and died after surgery.
Disease progression remained unaffected after surgery for the three ambulatory patients who had cervical injections. Two of the patients died secondary to bulbar ALS, said Dr. Feldman.
The investigators analyzed ALS Functional Rating Scale (ALSFRS) scores for patients who had bilateral transplants. Patients had been tested at baseline and at nine months. At nine months after surgery, the curve of disease progression appeared to flatten, and ALSFRS scores were higher than would be expected for patients with ALS at a comparable stage of disease under traditional management, said Dr. Feldman.
Although the patient population was small, the data “suggest that transplantation in subjects early in the course of the disease with no bulbar signs clearly carries less risk,” said Dr. Feldman. “Whether or not there’s a benefit, we simply do not know,” she added.
Enrollment has begun in a phase II trial of the stem cell transplantation procedure. Patients will receive bilateral injections of two million stem cells. Three future cohorts will receive four million, six million, and eight million stem cells, respectively. A final cohort will receive bilateral lumbar and bilateral cervical transplants, said Dr. Feldman.
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