Long-term Clinical and Safety Outcomes from a Single-site Phase 1 Study of Neural Stem Cell Transplantation for Chronic Thoracic Spinal Cord Injury

Academic Background

Spinal cord injury (SCI) is a severe neurological condition that causes significant disability in millions of people worldwide. Traditional treatments primarily focus on stabilizing the injury, preventing further damage, and helping patients regain some function through rehabilitation. However, the efficacy of these methods is limited, especially for patients with chronic SCI, where the likelihood of functional recovery is lower. In recent years, neuromodulation and cell-based therapies have emerged as new hopes for SCI treatment. Among these, neural stem cells (NSCs) are considered a promising approach due to their potential to differentiate into various neural cell types.

This study aims to evaluate the long-term safety and clinical efficacy of a neural stem cell line called NSI-566 in patients with chronic thoracic SCI. NSI-566 is a neural stem cell line derived from human fetal spinal cord tissue and has been approved by the U.S. Food and Drug Administration (FDA) for clinical trials. Previous studies have shown that NSI-566 exhibits good safety and some functional recovery in animal models. However, its long-term effects in human patients have not been fully validated. Therefore, this study conducted a 60-month follow-up of four patients with chronic thoracic SCI to assess the safety and potential therapeutic effects of NSI-566 transplantation.

Source of the Paper

This paper was co-authored by Joel R. Martin, Daniel Cleary, Mickey E. Abraham, and others from the Departments of Neurological Surgery, Regenerative Medicine, and Anesthesiology at the University of California, San Diego. The paper was published on December 17, 2024, in the journal Cell Reports Medicine, titled “Long-term clinical and safety outcomes from a single-site phase 1 study of neural stem cell transplantation for chronic thoracic spinal cord injury.”

Research Process

1. Study Design and Patient Screening

This study is a single-center Phase 1 clinical trial designed to evaluate the safety and feasibility of NSI-566 neural stem cell transplantation in patients with chronic thoracic SCI. The study enrolled four patients who met the following criteria: SCI duration between 1 and 2 years, ASIA-A grade (complete SCI), and injury level between T2 and T12. All patients received intraspinal injections of NSI-566, and no control group was included.

2. Preparation and Transplantation of NSI-566 Neural Stem Cells

The NSI-566 neural stem cell line was derived from the spinal cord tissue of an 8-week gestational age fetus, and the preparation process complied with the National Institutes of Health (NIH) and FDA Good Tissue Practice Guidelines. The cells were thawed one day before surgery and washed to remove the freezing medium, ultimately being reconstituted into a suspension of 2×10^6 cells per milliliter. During the transplantation surgery, NSI-566 cells were injected into the remaining tissue lateral to the injury site using a customized stereotactic injection device, with a dose of 2×10^5 cells per injection site.

3. Postoperative Follow-up and Evaluation

Postoperatively, patients were followed up for 60 months, with assessments including the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scores, Spinal Cord Independence Measure (SCIM) scores, pain scores, electromyography (EMG), and Brain Motor Control Assessment (BMCA). Additionally, spinal cord morphology and functional changes were monitored using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).

Main Results

1. Safety Assessment

Among the four patients who received transplantation, a total of 65 adverse events were recorded, with only one serious adverse event (SAE). This event involved a patient who died from sepsis related to a sacral ulcer 30 months post-transplantation, which was deemed unrelated to NSI-566 transplantation or surgery. No tumor growth or immune rejection related to the transplantation was observed in any patient.

2. Neurological Improvement

Two patients (001 and 010) showed neurological improvement post-transplantation, including increased motor and sensory scores. Patient 001 exhibited a two-level improvement in sensory and motor function six months post-transplantation, but this improvement decreased to one level after 27 months. Patient 010’s improvement remained stable. Additionally, EMG showed new muscle activity in three patients, indicating neurological recovery.

3. Pain and Quality of Life

Two patients (001 and 006) experienced a reduction in pain scores post-transplantation, and their quality of life scores remained stable. However, patient 008 showed a significant decline in quality of life scores due to a sacral ulcer.

4. Imaging Assessment

MRI and DTI imaging showed no new edema or fluid accumulation at the injury site, and the morphology of the spinal cord tracts remained stable, with no significant remodeling or improvement observed.

Conclusion

This study is the first to validate the long-term safety and potential efficacy of NSI-566 neural stem cell transplantation in patients with chronic thoracic SCI. The results demonstrate that NSI-566 transplantation is safe, and some patients showed neurological improvement post-transplantation. Although these improvements did not translate into significant functional recovery, the study provides important reference data for future dose-escalation studies and larger-scale clinical trials.

Research Highlights

1. Long-term Safety Validation: This study is the first to conduct a 60-month follow-up of NSI-566 neural stem cell transplantation, validating its long-term safety.
2. Neurological Improvement: Some patients showed improvements in motor, sensory, and EMG activity post-transplantation, indicating the potential of NSI-566 to promote neural regeneration.
3. Pain Relief: Two patients experienced a reduction in pain scores and improved quality of life.
4. Imaging Assessment: MRI and DTI imaging showed stable spinal cord structure post-transplantation, with no new complications.

Research Significance

This study provides important clinical data on neural stem cell transplantation for chronic SCI, demonstrating the safety and potential efficacy of NSI-566. Although the study has a small sample size and no control group, its results lay the foundation for future dose-escalation studies and larger-scale clinical trials. Additionally, the study suggests that neural stem cell transplantation may become a new treatment option for patients with chronic SCI, with significant scientific and clinical value.