I haven’t written in a long time but needed to share that little piece of news… that is bringing great joy to my heart. I am impatiently waiting for the results… I hope it went well:
U.S.: FDA-approved NSI-566 Phase II trials commenced in September 2013, and concluded final surgeries in July 2014. Phase II concludes after six-month observation period.
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 Trials
Neuralstem concluded final surgeries in the company’s NSI-566/ALS Phase II trials in July 2014. This phase of the study will conclude after a six-month observation period. The Phase II trials were approved by the FDA to commence in April 2013, upon conclusion of the Phase I FDA-approved trial to test the safety of the neural stem cells and transplantation surgery in patients with ALS in February 2013. The National Institutes of Health and ALSA committed to generous grants in funding for the Phase II 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 were designed to treat up to 15 patients, in five different dosing cohorts. The final cohort have received a total of 16 million NSI-566 neural stem cells, through 40 surgical injections of 400,000 cells per injection. (Phase I maximum was 15 injections of 100,000 cells each.) All of the patients were ambulatory and resided within close geographic proximity to the research center where they participated. 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 underwent lumbar transplantation and returned for the cervical treatment during a second 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 concluded six months after the final surgery.