Clinical trials using neural stem cells

Neural stem cells (mouse)

Allogeneic (single donor) neural stem cells are being investigated for their potential in treating spinal cord injuries. There are several clinical trials examining human neural stem cells in spinal cord injuries (see These trials inject neural stem cells directly into the spinal cord with the hope that the cells help re-establish some of the connections between neurons and create the necessary cells to support both the old and new neurons.

In December 2010 the Swiss regulatory agency for therapeutic products approved a StemCell Inc. sponsored Phase I/II clinical trial on chronic spinal cord injury at the Balgrist University Hospital in Zurich (Switzerland). The trial used specific stem cells derived from human brain tissue (neural stem cell or NSCs), which can make any of the three major kinds of neural cells found in the central nervous system. The trial was based on preclinical evidence that oligodendrocyte cells were replaced after transplanting human NSCs into in a particular mouse model for spinal cord injuries. For the trial, human NSCs (specifically referred to as Human Central Nervous System Stem Cells or HuCNS-SC) were directly implanted into the spinal cord of patients with complete and incomplete chronic thoracic spinal cord injuries. This trial was officially completed in June 2015 ( identifier no. NCT01321333). In 2012 a further Phase I/II clinical study of HuCNS-SC cell transplantation was started with 12 subjects ( identifier no. NCT01725880) and in 2014 another clinical trial was started to test the safety and efficacy of HuCNS-SC transplantation in cervical spinal cord injuries ( identifier no. NCT02163876). After having treated 12 patients in the NCT01321333 phase I/II trial and additional 31 in the NCT02163876 phase II trial (total 43 patients) the company reported no serious adverse effects. However, Stem Cell Inc. prematurely terminated its stem cell programmes in 2016 following an in-depth review of data from these studies. The outcomes appear to have been safe, but were not as effective as the company was aiming for. Stemcells Inc. is the second high-profile cellular therapy developer to fall short in the highly challenging neural therapies space in recent years.

In 2014 Neuralstem began a Phase I safety trial of its NSI-566 neural stem cells for chronic spinal cord injury at the University of California, San Diego School of Medicine ( identifier no. NCT01772810). This trial uses the same cells and a similar procedure as the companys Amyotrophic Lateral Sclerosis (ALS) trials (the first FDA-approved neural stem cell trial for the treatment of ALS). The 2014 trial will include a total of 8 patients, four of whom have thoracic spinal cord injuries causing complete loss of sensory and motor function. This trial is currently recruiting with an estimated completion of treatments in 2018 and study results in 2022.

The Miami Project clinical researchers currently have several clinical trials and clinical studies available for people who have had a spinal cord injury; some are for acute injuries and some are for chronic injuries. The clinical trials are testing the safety and efficacy of different cellular, neuroprotective, reparative, or modulatory interventions. These include a Phase I clinical trial with patients own myelinating cells, cells derived from the peripheral nervous system Schwann cells ( identifier no. NCT01739023). The Miami Project is also sponsoring a Phase I clinical trial of autologous human Schwann cell (ahSC) transplantation in participants with chronic spinal cord injuries ( identifier no. NCT02354625). While the former trial was completed in 2017, the latter is currently recruiting - approximately until January 2019.

Mesenchymal/stromal stem cells are being investigated as possible treatments for spinal cord injuries. Clinical Trials ( identifies at present total of 16 trials tagged as MSC trials in spinal cord injuries. These include studies that investigate the safety and efficacy of MSCs derived from the patients own bone marrow (9), adipose tissue (fat) (5) or cord blood (2). MSCs are injected in a number of different ways in these trials - including directly into the spinal cord or the lesion itself, intravenously, or even just in the skin. The hope is that when transplanted into the injured spinal cord, these cells provide tissue protective molecules and help to re-establish some of the circuitries important for the network of nerves (indirectly from cell integration and differentiation). More information can be found here.

California based biotech Geron had a widely reported clinical trial under way for a treatment the first of its kind involving the injection of cells derived from human embryonic stem cells. The injected cells were precursors of oligodendrocytes, the cells that form the insulating myelin sheath around axons. Researchers hoped that these cells, once injected into the spinal cord, would mature and form a new coating on the nerve cells, restoring the ability of signals to cross the spinal cord injury site.

After treating four patients with these cells in a Phase I clinical trial and reporting no serious adverse effects, Geron announced in November 2011 it was discontinuing its stem cell programme. The company said stem cells continue to hold great promise, but cited financial reasons for shifting focus to other areas of research.

Following up on the cellular technology initially developed by Geron, Asterias Biotherapeutics has developed a program that focuses on treating spinal cord injuries with specially developed oligodendrocyte progenitor cells (OPCs), precursors of oligodendrocytes. These cells, known as AST-OPC1, are produced from human embryonic stem cells. The hope is that when transplanted into the injured spinal cord abruptly after injury (7-14 days), OPCs may re-myelinate and restore lost functions.

In a Phase I clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered embryonic stem cell-derived OPCs at the site of injury. Delivery of OPCs was successful in all five subjects and no serious adverse events were associated with either the administered cells or the accompanying immunosuppression regimen. In four of the five subjects, MRI scans suggested a reduction in the volume of spinal cord injury.

A second follow up (dose escalation) Phase I/II trial with AST-OPC1 in acute (14-30 days after injury) sensorimotor complete cervical spinal cord injuries is currently recruiting participants ( identifier no. NCT02302157).

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