Two patients afflicted with amyotrophic lateral sclerosis have received stem cell injections into their spinal cords at the University of Michigan Health System. These are the first two subjects in a national clinical trial.
Both of these volunteers have returned home and will continue to receive medical follow-up and monitoring in order to assess the safety of this procedure and to detect any potential improvements in the condition of these patients.
Additional patients with this condition, which is also known as Lou Gehring’s disease, are being evaluated for possible participation in the trial at U-M and Emory University. This phase 2 trial is approved by the US Food and Drug Administration (US FDA) and is being funded by a Maryland-based company called Neuralstem, Inc., the proprietor of this stem cell product.
Neuralstem, Inc., has developed a neural stem cell line called NSI-566. When injected into the central nervous system of a living animal, these cells will divide up to 60 times and differentiate into a variety of neural cells (neurons, glial cells, etc.). Several publications have shown that injected NSI-566 cells survive when injected into the spinal cord, differentiate into several different neural cell types, and successfully integrate into the presently existing neural network.
In ALS patients, motor neurons progressively die off in the spinal cord, which limits voluntary movement. ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to complete paralysis, and eventually, death. According to the ALS Association, as many as 30,000 Americans have the disease, and about 5,600 people in the U.S. are diagnosed with ALS each year. The goal of this treatment strategy is to stabilize ALS patients and to replace dead or dying neurons and to slow the progressive decline and loss of movements, walking, and eventually breathing.
Eva Feldman, professor of neurology at the U-M Medical School, is the principal investigator for this clinical trial, and serves as an unpaid consultant to Neuralstem, Inc. Dr. Feldman led the analysis of the results from the Phase 1 trial, which ended in 2012. In this Phase 1 trial, 100,000 cells were delivered to each patient, and the patients tolerated them well and experienced to severe side effects. One subgroup of patients seemed to experience interruption of the progression of ALS symptoms.
Feldman commented, “We’re going to be permitted to give more injections and more stem cells, in Phase 2. We’re very excited that we have been able to bring this important work to the University of Michigan.”
Parag Patil, a neurosurgeon and biomedical engineer, performed both operations on the trial participants. In each case, the patient’s spinal column was unroofed and the spinal cord exposed to receive the cells. The stem cells are then introduced by means of 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, as assistant professor, also serves as a paid engineering consultant to Neuralstem, Inc., in order to further prefect the injection device. A third participant in this clinical trial received a stem cell injection in September at Emory University in Atlanta, Georgia. This Phase 2 dose escalation trial is designed to treat up to 15 ambulatory patients in five different dosing cohorts, and will do so under an accelerated dosing and treatment schedule. The first 12 patients will be divided into four cohorts and each 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 stem cells per injection. The trial will now progress to a maximum of 20 cervical injections of up to 400,000 stem cells per injection. The last three Phase 2 patients will receive injections into the cervical and lumbar spinal regions, and will receive 20 injections of 400,000 cells in the lumbar region in addition to the cervical injections they have already received. The trial also accelerates the treat schedule, and is designed to progress at the rate of one cohort per month with one month observations periods between cohorts. Researchers expect all of the patients could be treated by the end of the second quarter in 2014.