Our Clinical Approach
Our clinical approach is based on a vision that homologous transplantation of tissue-derived "adult" (non-embryonic) stem cells is the most natural, promising and viable path to harnessing the therapeutic potential of neural stem cells. We believe that a single neural stem cell transplantation might lead to a long-term therapeutic benefit.
Our therapeutic premise is to transplant CNS-derived stem cells for the treatment of CNS disorders — i.e., a homologous approach. These multi-potent, tissue-derived “adult” stem cells are naturally programmed to become mature functional CNS cells and can be directly transplantable into the brain, spinal cord or eye.
Conversely, embryonic stem (ES) and induced pluripotent stem (iPS) cells have the potential to differentiate into any of the various cell types of the body by undergoing careful re-programming or genetic modification. Approaches using ES or iPS cells need to limit the number of undifferentiated cells that might be transplanted along with the intended target therapeutic cell.
Cells, tissues or organs for transplantation may be either autologous (derived from the patient) or allogeneic (donor-derived). Cells derived from patients (autologous) might first need to be genetically modified or corrected to eliminate the inherent disease or disorder. Our purified allogeneic human neural stem cells, derived from healthy donors, are ready for use without modification, and therefore offer a less complicated and more feasible cellular approach as compared to ES and iPS cell platforms.
Scalable and Bankable “Stem Cells in a Bottle”
Our cryopreserved banks of human neural stem cells can be produced at commercial scale as “stem cells in a bottle,” then distributed for patient doses as needed, much like an off-the-shelf pharmaceutical product. In contrast, autologous stem cells derived directly from the patient and then administered back into the same patient requires a costly personalized process in which the cells are grown and expanded on an individual basis. Autologous based approaches may therefore not be practicable or feasible for timely therapeutic interventions as compared to banked allogeneic cells ready for transplantation.
Validating Our Approach in the Clinic
Extensive pre-clinical data has shown that our human neural stem cells engraft, migrate and differentiate appropriately after transplantation into the normal cell populations found in the CNS. We are now engaged in trials to validate our approach in the clinic.
Safety and tolerability: We have demonstrated the safety and tolerability of both our HuCNS-SC® cells and the transplantation procedure in clinical trials in the brain, the spinal cord and the eye.
Our Phase I clinical trial in neuronal ceroid lipofuscinosis (NCL), also referred to as Batten disease, initiated in 2006, was the first ever FDA-authorized clinical trial of human neural stem cells. Data from this landmark trial, reported in June 2009, demonstrated the clinical safety and tolerability of the cells, and included evidence of engraftment and long-term survival of the donor cells. Our Phase I trial in Pelizaeus-Merzbacher disease (PMD), completed in 2011, as well as our Phase I/II clinical trials in spinal cord injury (SCI) and age-related macular degeneration (AMD), both completed in 2014, have shown additional clinical evidence of safety and tolerability in a wide range of human subjects.
Preliminary efficacy: Our Phase I/II clinical trials in SCI and AMD have also resulted in favorable evidence of preliminary efficacy, thereby adding support for advancement to our Phase II proof-of-concept studies currently underway in both of these indications.
Long-term survival: Data gathered from our Phase I trial in NCL has provided evidence that our HuCNS-SC cells survive and migrate following transplantation into the brain Importantly, our clinical data also indicates that our HuCNS-SC cells can persist long-term after immunosuppression treatment is discontinued. This clinical data supports our belief that the CNS is "immune-privileged" and that a relatively brief period of immunosuppression following transplantation may be all that is required to support long-term donor cell survival.