Transplant of Human Neural Stem Cells into ALS Patients Found Safe in Phase 1 Trial

Injection of human neural stem cells into the spinal cord of people with amyotrophic lateral sclerosis (ALS) was found safe and did not cause adverse effects even two years after the transplant, results from a Phase 1 clinical trial show.

Trial findings were published in the study, “Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome,” in the journal Stem Cells Translational Medicine.

Human neural stem cells (hNSCs) are able to integrate brain tissue and promote tissue regeneration. These cells have shown potentially beneficial effects in preclinical animal models of neurological diseases, but very few studies have assessed its feasibility in human patients.

The Phase 1 trial (NCT01640067) evaluated the safety (as its main objective) and feasibility of injecting human neural stem cells into the spinal cord of ALS patients.

Researchers isolated human neural stem cells from two miscarried human fetuses, which were then expanded in the lab prior to injection.

“Our study is the first to use medical transplantation of stable, clinical‐grade hNSC lines that are isolated from brain biopsies from fetuses that are miscarried, and that can be reproducibly and stably expanded ex vivo,” the researchers wrote.

The trial included 18 ALS patients, five women and 13 men, with a median age of 48 years. Patients were followed for a median of 24 months after the cells were implanted.

During this period, no patients reported severe adverse effects, and only one patient reported mild painful spasms in the lower limbs. A common adverse effect was pain after surgery, but was confined to the implant site and lasted 18 days on average.

“Our results underscore that micro-transplantation of cells into the human anterior spinal cord is a safe procedure, even when performed in subjects as fragile as patients with ALS,” the researchers wrote.

Imaging analysis using magnetic resonance showed there was an expected accumulation of extradural fluid at the surgery site that was resolved spontaneously within three to six months. No structural changes were observed for the brain and spinal cord of patients compared with images at the start of the study.

From the initial group, 11 patients died during follow-up due to the natural progression of ALS disease. Two patients underwent a tracheostomy due to progressive respiratory failure.

According to researchers, the treatment did not worsen the ALS progression in any patient. They did detect a temporary slowing of disease progression as shown by stabilization in some patients and improvement in others of scores on the ALS Functional Rating Scale Revised (ALS-FRS-R)  within the first month after transplant, continuing for up to four months.

Moreover, five patients reported a transitory functional improvement in ambulation and four patients in activities such as cutting food and handling utensils, handwriting, dressing, and hygiene. No statistically significant differences were detected in the forced vital capacity, a measure of lung function, nor in survival.

These results support the need to further assess the potential of human neural stem cells in a Phase 2 trial to continue to assess the cell’s safety as well as its efficacy.

“Our results support the use of [good manufacturing practice]-grade fetal hNSCs derived from in utero spontaneous death in future efficacy-seeking clinical trials for treatment of ALS,” the researchers wrote.

However, “substantial challenges remain to be addressed and resolved in upcoming phase IIa/IIb trials, including determination of the optimal number of cells to be injected, how long the cells remain active in humans, the criteria for patient selection, biomarkers for monitoring the disease course, and efficacy of the hNSCs,” they concluded.