These are indeed exciting times for spinal cord injury (SCI) clinical trials. There are trials ongoing around the world targeting different repair strategies. In this article we want to take the opportunity to explain some of the high profile clinical trials ongoing in the United States utilizing cells as a therapeutic intervention.
As many of our readers know, The Miami Project’s 1st Phase I clinical trial testing Schwann cells began in November 2012 and we are happy to announce that the final participant was transplanted in August 2015. Schwann cells come from your own body and they are a type of cell found throughout the entire peripheral nervous system (PNS). The PNS includes all nerves going out to muscles as well as sensory nerves coming from the muscles back to the spinal cord. Schwann cells are a type of “support” cell in the PNS and some important points about Schwann cells are that they 1) insulate (myelinate) individual nerve fibers (axons), which is necessary for sending appropriate electrical signals throughout the nervous system, 2) are not stem cells, they are adult cells and can only be Schwann cells, and 3) can be obtained from each person’s own body thereby eliminating the need for immunosuppression medicine.
This trial is specifically targeting people with new SCI, less than 30 days after injury, having sustained a trauma-induced lesion between thoracic levels T3-T11 and whom were neurologically complete. This is a dose escalation treatment trial, meaning that we will test 3 different doses: 5 million, 10 million, and 15 million Schwann cells. There were a total of 39 people screened for eligibility, 9 were enrolled, and 6 participants were transplanted. The first two participants received the 5 million cell dose, the second two received the 10 million cell dose, and the final two received the 15 million cell dose. Thus far, there have been no treatment-related adverse effects in any of the transplanted subjects, which is excellent news. Remember, safety is the determinate of success for this phase I trial. We are not releasing any other information about the participants or results because the trial is still ongoing and we cannot compromise the data. After the final participant is 12 months post-transplant we will prepare the results for publication in a peer-reviewed scientific journal.
Our 2nd Phase I clinical trial began in February 2015 for chronic SCI and will also be primarily focused on safety, but in addition it will involve a preliminary evaluation of the efficacy of combining Schwann cells with exercise and rehabilitation. For humans with chronic SCI, we hypothesize that axons might show improved function if myelin repair is induced with the implantation of autologous Schwann cells. In addition, spinal cord cavitation may be reduced and neural sprouting and plasticity may be enhanced via neurotrophic effects. In this trial, participants will receive three months of fitness conditioning and locomotor rehabilitation prior to transplantation in order to validate the stability of their neurological baseline as well as to enhance their fitness level thereby reducing any deconditioning effects. They will also receive fitness conditioning and rehabilitation for six months post-transplantation to maintain health and promote neuronal activity and potential neuroplasticity. We believe that this combination of cell therapy with intense rehabilitation prior to and following cell transplantation will enhance our chances of seeing improved recovery in the chronic setting https://clinicaltrials.gov/ct2/show/NCT02354625 .
Drs. Allan Levi and Kim Anderson, along with several other University of Miami faculty members, are also participating in a clinical trial testing a different cell therapy – neural stem cells. That trial, referred to as the Pathway Study, is sponsored by a company called StemCells, Inc.
The Pathway Study is testing the safety and potential benefit of a very specific stem cell type known as a neural stem cell; these are not Schwann cells. The neural stem cells being used in the Pathway Study were derived from fetal brain tissue and have the ability to self-renew and become the main types of mature cells found both in the brain and spinal cord. These cells do not come from your own body, therefore anyone who receives them into their body has to be on immunosuppression medicine. Studies of SCI in animals have shown that these human neural stem cells can survive and lead to recovery of function through remyelination and possibly neuronal cell replacement.
Prior to the Pathway Study, the company conducted a Phase I/II safety & preliminary efficacy clinical trial in humans with thoracic SCI. Twelve participants were transplanted within 3 to 12 months of injury. The results they have disclosed at scientific meetings indicate that neural stem cell transplantation appears to be safe; several participants have regained some sensation.
The Pathway Study is a larger Phase II efficacy clinical trial designed to determine if neural stem cells can help people with cervical SCI recover spinal cord function and gain strength and sensation. They will enroll up to 52 participants. Individuals may be able to join the study if they are 18 to 60 years old, have a cervical SCI that is classified as ASIA Impairment Scale grade A, B, or C, are less than two years post-injury, and are generally in good health. Individuals that are eligible for the study will participate for approximately 12 months. There are several sites around the country that are enrolling https://clinicaltrials.gov/ct2/show/NCT02163876 .
Many of you have probably heard of the Geron clinical trial that was prematurely halted a few years ago for financial reasons. In 2013, a new company called Asterias Biotherapeutics took over the rights for everything related to the prior trial. The first trial was a Phase I safety trial using a human embryonic stem cell line pre-differentiated into oligodendrocyte progenitor cells. The oligodendrocyte progenitor cells are targeting reduction of the size of the injury cavity as well as remyelination of demyelinated axons to restore conduction. These cells also cannot be obtained from your own body, hence require immunosuppression medicine as well when administered to anyone. In that trial, 5 individuals with complete thoracic injury received the cells within 14 days after their injury. The results they have disclosed at scientific meetings indicate that the cell transplantation appears to be safe and that four of the five participants appear to have a smaller cavity when evaluated by MRI.
In 2015, they began a Phase I/IIa dose escalation trial, the SCI-Star study. This trial is enrolling individuals with cervical injury between levels C5-C7 whom are neurologically complete. The cells have to be injected between 14 to 30 days post-injury; up to 13 participants will receive the cells. There are at least 3 centers enrolling https://clinicaltrials.gov/ct2/show/NCT02302157 .
The final cell therapy of high profile is being conducted by a company called Neuralstem. This is a Phase I safety trial using human fetal spinal cord neural precursor cells. These stem cells are targeting growth factor replacement and possibly neuronal cell replacement. Again, because these cells do not come from one’s own body, they require immunosuppression medicine. The company previously completed a Phase I safety trial using the same cells in individuals with Lou Gehrig’s disease. They transplanted 18 participants in mid- to late stages of the disease and demonstrated safety. The company then obtained approval for the SCI Phase I trial. A total of 4 participants with complete thoracic injury, between one and two years post-injury, will be transplanted. The study procedures are all performed in California https://clinicaltrials.gov/ct2/show/NCT01772810 .
To find out more information about the trials being conducted at The Miami Project, contact The Miami Project Education Department at 305-243-7108 or MPinfo@med.miami.edu . More information about all of our clinical trials and studies is available at http://www.themiamiproject.org/trials .