Clinical translation of human neural stem cells, promise for the future
Authors: Tsukamoto-Weissman Ann 
Published: March 2012

Currently, there are few effective therapies for the treatment of neurodegenerative diseases or injuries to the brain, spinal cord and eye. Human neural stem cell transplants offer the prospect to treat such conditions and represent a potential exciting new medical therapy. A highly purified composition of human neural stem cells has been isolated, expanded and stored as banks of cells, HuCNS-SC®. When transplanted into the brain of immunodeficient rodents, human neural stem cells reside and proliferate in host neurogenic sites, such as the subventricular zone and dentate gyrus of the hippocampus. Their progeny migrate globally throughout the brain and differentiate in a site-appropriate manner into neurons, astrocytes and oligodendrocytes. When transplanted into the spinal cord above and below the injury site, these cells also migrate extensively and differentiate, remyelinate and make synaptic connections with host neurons. HuCNS-SC have also been shown to produce soluble proteins such as housekeeping lysosomal enzymes, neurotrophic factors, and chemokines which may protect damaged host cells and also become mature oligodendrocytes which myelinate dys- or demyelinated host axons. Moreover, these human cells survive long-term in the host brain with no signs of tumor formation or adverse effects and unlike ESC or iPSC, HuCNS-SC do not require pre-differentiation prior to transplant nor do they form teratomas. Therefore, a single transplant of human neural stem cells offers the prospect of a durable clinical benefit. Studies transplanting HuCNS-SC into animal models of human diseases or injury have been performed to assess the cells’ biological properties including their impact on these specific targets. These preclinical efficacy studies have demonstrated protection of host cells and/or improvements in specific functional deficits and provided the foundation for the neuroprotection and neural replacement strategies to support initiation of our clinical studies. Three clinical studies have been initiated to date. The first clinical study in Batten disease, a fatal lysosomal storage disease, has been completed and the surviving patients are now ~4-5 years post-transplant with no safety concerns. A trial in PMD, a fatal myelination disorder, is completing and will examine evidence of de novo myelin formation from transplanted HuCNS-SC. A trial in chronic spinal cord injury has completed dosing of the most severely injured patients and will now enrol those with incomplete thoracic injuries. The Company has recently filed regulatory documents to begin a trial in dry AMD. Preclinical studies in a rat model of retinal degeneration, the RCS rat, have shown cone photoreceptor protection following subretinal transplants of HuCNS-SC. The clinical data derived from these studies should facilitate future clinical testing of HuCNS-SC cells in a broad range of other neurological disorders including Alzheimer’s disease, stroke, and cerebral palsy. In addition to its pioneering efforts in the discovery and development of its proprietary human neural stem cell, the Company’s scientists have also identified a rare cell population from non ideal human adult livers that display the key hallmarks of a therapeutic product for treating liver diseases. Efforts are underway to define optimal expansion conditions to create cell banks of liver-engrafting cells.