HUMAN TRIALS TO BEGIN
SCS INTRODUCTION
Well, here it is. This is what we have been working toward for more than
20 years, human cure trials on the main problem itself. There have been
many treatments and trials on the side effects of SCI, but this is our
first one on human patients and the world's first so far as we know,
which will use autologous transplants. If they would like to be
considered for participation members in the SCS Data System should
notify us in Writing Their data form will then be forwarded to Cedars-
Sinai. This trial is in the process of final approval by the Human
Research Committee of Cedars- Sinai hospital in Los Angeles, California.
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PROTOCOLS (by Michel F. Levesque, M.D. and Thomas Neuman, Ph.D.)
Spinal Cord Society currently supports the research project at the
Cedars-Sinai Medical Center. Los Angeles, that is aimed to initiate
clinical trials on cell therapy of chronic spinal cord injury using stem
cell derived neurons from the CNS.
Current status of the clinical trials:
The purpose of this study is to determine the safety. reliability and
effectiveness of CNS stem cell transplants for the possible restoration
of spinal cord function after spinal cord injury. Neural transplantation
has been used in the last 10 Years in numerous animal studies for the
experimental treatment of spinal cord injury. Several publications have
reported very encouraging results using fetal neurons. which are nerve
cells taken from a human embryo. and more recently, neuronal stem cells,
which are present in the adult brain and under certain conditions are
able to become functional neuronal cells. But the effective- ness and
long term results of tissue transplantation in the spinal cord injury
patients is unknown and should be considered investigational.
The research laboratory at the Neurofunctional Surgery Center has
developed two different approaches to neuronal transplantation: 1.
Autologous transplantation, 2. Transplantation using cells isolated from
other individuals (homologous transplantation). In the clinical trials
we will use either autologous neuronal cells isolated from the patient's
own nervous system or central nervous system stem cell lines from our
laboratory cell bank.
Autologous transplantation. If patients favor autologous cell
transplantation then we have to obtain a small fragment of brain tissue
from the hippocampus or cerebral cortex during a brain biopsy procedure
which has to be done 3-4 months before transplantation surgery. We will
isolate stem cells from this brain tissue. propagate these cells, and
differentiate them into several neuronal cell types which will then be
used to reconstruct the spinal cord in the site of in- jury. Such
autologous (same patient) transplantation does not require the use of
immunosuppressant to avoid rejection of transplanted cells.
Homologous transplantation. The alternative to autologous
transplantation will be transplantation of nerve cells derived from
embryonic or adult nervous system stem cell lines developed in our
laboratory and kept in the stem cell bank. Homologous trans- plantation
does require use of immunosuppressant to avoid rejection of transplanted
cells.
The tissue transplantation procedure is performed in two stages. the
first stage, physicians will use an MRT (magnetic resonance imaging) or
CT (computed tomography) scan to determine the proper location for the
implants within your spinal cord. In the second stage, cell
transplantation is performed under general anesthesia. The spinal cord
will be exposed after posterior laminectomies, a surgical procedure
removing the bony midlines of the spine. The cell suspension will be
introduced using a stereotactic microsyringe at regular 1-2mm spacing
above and below the level of injury bilaterally by entering along the
dorsal columns aiming at the anterior horns. At the level of injury, the
central cavitation will be filled with the cell suspension.
Possible Risks:
For the contemplate surgery, the risk of death is ap- proximately 1-2%
and the risk of morbidity (dam- age) such as meningitis, CSF leakage,
hemorrhage, is approximately 5%.
The risks associated with general anaesthesia, wound infection, etc. are
the same as for any major spinal procedure and are considered minimal
(1-2%). Al- belt difficult to project, the incidence and possibility of
transmission of a virus, bacteria, fungus or other microorganism by
implantation of tissue must be considered. However, the risk of such
transmission is considered minimal (1-2%) because all the trans- planted
tissue will be checked prior to implantation for hepatitis, HIV, herpes,
etc.
Patient selection:
Patients enrolled in this protocol should have:
1. a confirmed diagnosis of spinal cord injury be- low spinal thoracic
level T2,
2. evidence of complete or incomplete paraplegia with bladder and
bowel dysfunction,
3. a stable thoraco-lumbar spine following surgical stabilization,
4. no extra-spinal compression from hematomas or bony fragments.
Specific contraindications for inclusion in this study include severe
hypertension needing pharmaceutical or other therapy; renal, liver,
cardiac or other major organ disease; cancer; and other significant
illnesses. Every patient enrolled in this protocol will undergo a
neurological evaluation, a rehabilitation evaluation and an anesthesia
evaluation. The initial study will consist of twenty four surgical
patients. No new participants will be considered until at least three
months following the initial patients' surgeries. The study will be done
over a two year period. All patients will be volunteers.
A postoperative MRI scan will be performed on the following days and the
patients will be transferred to the intensive care unit for an
anticipated 24-hour stay. No particular side effects are anticipated,
al- though this is still a relatively new procedure. Each patient will
receive antibiotics prophylactically on the day of surgery and for three
days thereafter. The patient will be transferred to the rehabilitation
unit as soon as he or she reaches a stable medical condition.
Regulatory issues:
These clinical trials are experimental and require Cedars-Sinai Medical
Center Institutional Review Board (IRB) committee's approval. This
committee has accepted a preliminary proposal and a definite final
approval is currently pending related to language clarification and a
clear distinction between homologous and autologous transplantation.
The Food and Drug Administration (FDA) requires manufacturers of human
cell and tissue-based products to register with the agency before using
these products in any human treatments. We are in the process of
fulfilling the registration requirements and expect to finish this phase
of preparation for clinical trials in the nearest future.
Our original plan was to start clinical trials in June 1999, but due to
several delays in different phases of preparation for clinical trials,
including several regulatory issues, we plan to start patient selection
and production of transplantable cells in August 1999
Michel F. Levesque, M.D.
Department of Neurosurgery
Cedars-Sinai Medical Center
Toomas Neuman, Ph.D.
Director, Neurobiology
Cedars-Sinai Medical Center
Copyright SCS 1999 All rights reserved