Italian Sponsored Phase I Trial Transplants Human Neural Stem Cells into ALS Patients

human neural stem cells

A recent Phase 1 clinical trial involving the injection of human lateral sclerosis (ALS) was found safe and did not cause adverse effects even two years after the transplant.  Study results were published in the journal Stem Cells Translational Medicine as reported in ALS News Today.

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

The recent Phase I trial evaluated the safety and feasibility of injecting human neural stem cells into the spinal cord of ALS patients.  The team separate human neural stem cells from two miscarried human fetuses, which were thereafter expanded in the lab prior to injection.

The Trial

The study 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.  Apparently during the study no severe adverse events were reported; during the period one common adverse effects was pain after the surgery however this was confined to the implant site and persisted on average for 18 days.

The team utilized imaging analysis leveraging magnetic resonance—it depicted an expected accumulation of extradural fluid at the surgery site that was resolved spontaneously within three to six months. The study team observed no structural changes concerning the brain or the spinal cord of patients compared with images at the start of the study.

Out of the total patient group 11 patients died due to the natural progression of ALS disease. Two patients underwent a tracheostomy due to progressive respiratory failure.

Comments and Context

The team noted “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 treatment did not worsen the ALS progression in any patient reported the researchers. There was some detection of 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 within the first month after transplant, continuing for up to four months.

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.

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.

Lead Research/Investigator

Angelo L Vescovi, PhD, Fondazione IRCCS Casa Sollievo della Sofferenza, Advanced Therapies Production Unit