Neuralstem Cell Therapy for ALS
- Product status:
- U.S.: FDA-approved NSI-566 Phase II trials commenced in September 2013; Phase I safety trial ended in February 2013
- Mexico City: NSI-566 Phase I / II trial expected to commence in 2014
- Mechanism of Action: Rebuilding neural circuitry
- Route of Administration: Direct injections into the spinal cord
Neuralstem is seeking to treat the symptoms of ALS via transplantation of its NSI-566 human spinal cord stem cells (HSSCs) directly into the gray matter of the patient’s spinal cord. In ALS, motor neurons die, leading to paralysis. In preclinical animal work, Neuralstem cells both made synaptic contact with the host motor neurons and expressed neurotrophic growth factors, which are protective of cells. View published papers here: 1, 2, 3.
Neuralstem initiated the first FDA-approved stem cell trial for ALS in January 2010, at Emory University. This Phase I safety trial, to evaluate the safety of the NSI-566 cells and surgical technique, was designed to enroll up to 18 patients. The Principal Investigator is Eva Feldman, MD, PhD, Director of the A. Alfred Taubman Medical Research Institute, Director of Research of the ALS Clinic at the University of Michigan Health System, and President of the American Neurological Association. The Site Investigator is Jonathan Glass, MD, Professor of Neurology, Emory School of Medicine and Director of the Emory ALS Center. The trial was awarded an Orphan Drug Designation by the FDA in February 2011.
In humans, Neuralstem expects that the transplanted cells will:
- GRAFT permanently into the region where they were transplanted
- REBUILD circuitry with the patient motor neurons
- PROTECT patient neurons from further ravages of the disease
In a review of the safety data from the initial nine patients, Neuralstem cells were deemed to be safe, with no adverse reactions reported believed to be related to cells or surgical technique.
Neuralstem ALS Trial
Neuralstem received FDA approval to commence the NSI-566/ALS Phase II trials in April 2013, following conclusion of its Phase I FDA-approved trial to test the safety of its cells and transplantation surgery in patients with ALS in February 2013. The National Institutes of Health and ALSA have committed to generous grants in funding for this phase of the study.
The NSI-566/ALS Phase II dose escalation and safety trials commenced in September 2013, and expanded to three centers: Emory University Hospital in Atlanta, Georgia, site of Phase I; ALS Clinic at the University of Michigan Health System, in Ann Arbor, Michigan, and Massachusetts General Hospital in Boston. The trials are designed to treat up to 15 patients, in five different dosing cohorts, advancing up to a maximum of 40 injections, and 400,000 cells per injection based on safety. (Phase I maximum was 15 injections of 100,000 cells each.) All of the patients will be ambulatory and reside within close geographic proximity to the research center where they will participate. The first 12 patients received injections in the cervical region of the spinal cord only, where the stem cells could help preserve breathing function. The final three patients will undergo lumbar transplantation and then return for the cervical treatment during a second surgery. Each of these patients will then have received a total of 16 million NSI-566 neural stem cells, through 40 surgical injections of 400,000 cells per injection. The Phase II trials will conclude after an observation period of six months from the last surgery.
The Phase I safety trial enrolled 18 patients. The trial began with 12 late- to mid-stage patients who received a series of injections in the L2-L4 lumbar region. The first six patients were all non-ambulatory with permanent paralysis. Of these, the first three patients (Cohort A1) were treated with five unilateral cell injections, while the next three patients (Cohort A2) received ten bilateral injections in the same region. The trial then progressed to patients who were ambulatory. The first three of these (Cohort B) received five unilateral injections. The next three patients (Cohort C) received ten bilateral injections in the same lumbar region.
Neuralstem received approval from the FDA to move into the cervical (upper back) stage of the trial in the fall of 2011. The first of six patients in the cervical cohorts to receive stem cells was treated on November 18, 2011, which marked the first FDA-approved intraspinal surgical transplantation of stem cells into the cervical region. The trial then advanced to the final cervical cohort of three patients. The FDA approved the return of three patients from earlier cohorts to receive cervical transplants, making them the first to receive stem cell transplantation in both the lower and upper parts of their spinal cord. The first of these was treated in June 2012, and received five stem cell injections into the cervical region of the back, for a total of 15 injections, including the ten lower-back injections previously received. The last patient in the Phase I trial was treated in August 2012. The trial was designed as a safety trial to treat 18 patients, and conclude six months after the final surgery.
In Mexico City, Neuralstem is expected to commence an ALS Phase I / II trial in 2014.
- VIDEO FOX Medical Team In-depth Feature on ALS Patient Ted Harada and his second, the trial’s final, surgery of Neuralstem's ground-breaking Phase I stem cell trial (8/27/12). View Here
For more information on the trial:
- University of Michigan Health System, Ann Arbor http://www.umclinicalstudies.org/HUM00072488, http://www.pnrd.umich.edu
- Emory Healthcare, Atlanta (404) 778-7777 http://www.neurology.emory.edu/ALS/Support%20Our%20Center/active_trials/stem_cell_trial.html
- Interim Results of Phase I ALS trial:
- Abstract, NIH/National Center for Biotechnology Information (NCBI): "Lumbar Intraspinal Injection of Neural Stem Cells in Patients with ALS: Results of a Phase I Trial in 12 Patients." (March 2012) Here
- Presentation Poster, presented at American Neurological Association’s annual meeting (September 2011). Here
- Safety Study to use Electrical Impedance Myography (EIM) as a measurement tool in Neuralstem's ALS trials (April 2011). Here
- "Approaching Hope," by Nancy Ross-Flanigan, Michigan Alumnus magazine, Spring 2011. Here
For more information on ALS:
- The ALS Association www.alsa.org