StemCells, Inc. Initiates World’s First Neural Stem Cell Trial In Spinal Cord Injury

StemCells Inc Press Release
StemCells Inc announced today they are initiating a clinical trial using their fetal derived neural progenitor cells for the treatment of spinal cord injuries. Previously the company had reported that their stem cells, called HuCNS-SC, are capable of differentiating into various neural lineage cells including neurons, oligodendrocytes, and astrocytes. The fact that HuCNS-SC are derived from fetal sources allows them to possess a lower ability to stimulate immune responses, therefore, the cells can be used as an “off the shelf” product.
According to the company “The Company’s preclinical research has shown that HuCNS-SC cells can be directly transplanted in the central nervous system (CNS) with no sign of tumor formation or adverse effects. Because the transplanted HuCNS-SC cells have been shown to engraft and survive long-term, this suggests the possibility of a durable clinical effect following a single transplantation. StemCells believes that HuCNS-SC cells may have broad therapeutic application for many diseases and disorders of the CNS, and to date has demonstrated human safety data from completed and ongoing studies of these cells in two fatal brain disorders in children.”
The proposed study will be conducted at the Balgrist University Hospital, in Zurich, which is a private, non-profit institution managed in accordance with economic principles. The clinic has three key areas of expertise: it is a highly specialised centre providing examination, treatment and rehabilitation opportunities to patients with serious musculoskeletal conditions; it is responsible for training future doctors studying at the University of Zurich in orthopaedics and paraplegiology and providing professional training for doctors and medical staff in the domains of orthopaedics, paraplegiology, rheumatology, anaesthesiology and radiology; it is a research centre dedicated to improving quality for healthcare in the future. The number of patients or inclusion/exclusion criteria for the trial was not mentioned in the press release. However a look at reveals the following:
The study is a 12 patient Phase I/II trial in which treated patients will also receive immune suppression so that the transplanted cells will not be rejected. The trial has the following inclusion/exclusion criteria:
Inclusion Criteria:
• T2-T11 thoracic spinal cord injury based on American Spinal Injury Association (ASIA) level determination by the principal investigator (PI)
• T2-T11 thoracic spinal cord injury as assessed by magnetic resonance imaging (MRI) and/or computerized tomography (CT)
• ASIA Impairment Scale (AIS) Grade A, B, or C
• Minimum of six weeks post injury for the initiation of screening
• Must have evidence of preserved conus function
• Must be at stable stage of medical recovery after injury
Exclusion Criteria:
• History of traumatic brain injury without recovery
• Penetrating spinal cord injury
• Evidence of spinal instability or persistent spinal stenosis and/or compression related to initial trauma
• Previous organ, tissue or bone marrow transplantation
• Previous participation in any gene transfer or cell transplant trial
• Current or prior malignancy
Success in treatment of spinal cord injury has been reported in the peer reviewed literature by Cellmedicine in which a patient was treated with a combination of cord blood hematopoietic and placental matrix mesenchymal stem cells
The advantage of the approach proposed by StemCells Inc is that only one injection of stem cells may be necessary . The disadvantage is that while the stem cells may generate neurons, it is difficult to imagine how one source of stem cells alone can recapitulate and accelerate the multicellular process involved in healing of the spinal cord.
Treatment of spinal cord injuries using stem cells is also underway by the company Geron who uses embryonic stem cell derived oligodendrocytes in patients with spinal cord injury.
Two previous trials have been reported in the area of spinal cord injury that used mesenchymal stem cells exclusively. In 2006 the group of Movilgia et al from Argentina treated two patients with spinal cord injury using an interesting protocol of T cell plus MSC. Forty-eight hours prior to NSC implant, patients received an i.v. infusion of 5 x 10(8) to 1 x 10(9) AT cells. NSC were infused via a feeding artery of the lesion site. Safety evaluations were performed everyday, from the day of the first infusion until 96 h after the second infusion. Patient 1 was a 19-year-old man who presented paraplegia at the eight thoracic vertebra (T8) with his sensitive level corresponding to his sixth thoracic metamere (T6). He received two AT-NSC treatments and neurorehabilitation for 6 months. At present his motor level corresponds to his first sacral metamere (S1) and his sensitive level to the fourth sacral metamere (S4). Patient 2 was a 21-year-old woman who had a lesion that extended from her third to her fifth cervical vertebrae (C3-C5). Prior to her first therapeutic cycle she had severe quadriplegia and her sensitive level corresponded to her second cervical metamere (C2). After 3 months of treatment her motor and sensitive levels reached her first and second thoracic metameres (T1-T2). No adverse events were detected in either patient (Moviglia, G.A., et al., Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy, 2006. 8(3): p. 202-9).
Pal et al from Stemeutics in India reported 30 patients with clinically complete SCI at cervical or thoracic levels were recruited and divided into two groups based on the duration of injury. Patients with <6 months of post-SCI were recruited into group 1 and patients with >6 months of post-SCI were included into group 2. Autologous BM was harvested from the iliac crest of SCI patients under local anesthesia and BM MSC were isolated and expanded ex vivo. BM MSC were tested for quality control, characterized for cell surface markers and transplanted back to the patient via lumbar puncture at a dose of 1 x 10(6) cells/kg body weight. Three patients had completed 3 years of follow-up post-BM MSC administration, 10 patients 2 years follow-up and 10 patients 1 year follow-up. Five patients have been lost to follow-up. None of the patients have reported any adverse events associated with BM MSC transplantation (Pal, R., et al., Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study. Cytotherapy, 2009. 11(7): p. 897-911)
A search of for ongoing trials using stem cells in patients with spinal cord injury reveals the following:
1. Cairo University is performing a Phase I/II trial in 80 patients with spinal cord injury who are receiving autologous bone marrow derived stem cells. The trial includes patients that are treated with stem cells and receive physical therapy versus patients receiving physical therapy alone. The trial has completed enrollment and recruited patients who had injury 8 months to 3 years before entering the trial.

2. RNL Bio from Korea is performing a Phase I study on 8 spinal cord injury patients who had their injuries more than two months before entering the study. The cells administered are 40 million autologous adipose derived cells, given intravenously. The trial enrollment is completed and the Principle Investigator is Dr. SangHan Kim, MD from the Anyang Sam Hospital.

3. International Stemcell Services Limited from India is doing a 12 patient Phase I/II trial administering autologous bone marrow into patients after spinal cord injury. The trial enrollment is completed and the Principle Investigator is Dr.Arvind Bhateja, from the Sita Bhateja Speciality Hospital.

4. TCA Biosciences from Louisiana is performing a 10 patient Phase I trial using autologous bone marrow mesenchymal stem cells. The trial enrollment is completed.

5. The Memorial Hermann Healthcare System is doing a study using autologous bone marrow cells in children aged 1-15 using autologous bone marrow cells. The study plans to enroll 10 patients.

6. The Hospital Sao Rafael from Brazil is doing a 10 patient study using autologous bone marrow in spinal cord injury patients.
This exploration of tells us that relatively little is being performed in terms of stem cell therapy for spinal cord injury. Given the success of Cellmedicine at treating this condition, it will be interesting to see the outcomes of the other ongoing trials.

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