Unfortunately, applicability and value of such endpoints is oftentimes only evident after the trial is completed and many millions of dollars have been spent, highlighting the importance of a thorough and realistic reflection on endpoint selection. Therapeutic approaches using NSCs and other stem cell products
Venetoclax mouse for the treatment of CNS injury and disease fall into two broad categories, summarized in Figure 4: (1) regenerative/cell replacement to promote host tissue repair mechanisms and/or replace missing or damaged cells, and (2) therapeutic delivery to provide therapeutic macromolecules (enzymes, cytokines, neurotrophins, drugs, etc.) for neuroprotection, drug therapy, and/or stimulation of repair. A third clinically relevant approach is drug discovery via stem cell-based disease models. In this section we focus on regulatory approved stem cell-based CNS clinical trials, summarized in Table 1, Table 2 and Table 3, and include some preclinical studies that are considered close to IND. Stem cell therapies for neural transplantation and repair aim to replace damaged cells and/or promote host tissue local neural repair mechanisms, including neurogenesis, gliogenesis, and angiogenesis (see Table 1). Human NSCs derived from pluripotent
cells or extracted from CNS tissue can be used as undifferentiated cells, relying on the host signals to stimulate their proliferation and differentiation, or their lineage descendents can selleck compound be utilized, such as GRPs. The donor cells are typically delivered via stereotactic injection into the affected regions. An alternate means of cell replacement being developed is the recruitment of endogenous
neural progenitor cells from active adult germinal zones or relatively dormant progenitors elsewhere in below the CNS, as demonstrated in promising animal models of PD (Androutsellis-Theotokis et al., 2010). In 2010, two trials were authorized for the use of neural cells to treat SCI. Geron Corporation (Geron) received FDA clearance to initiate a phase I trial using hESC-derived oligodendrocyte progenitors (OPCs), GRNOPC1, in subacute thoracic SCI. This landmark study represents the first huESC-derived product for clinical testing. StemCells, Inc. (StemCells) received regulatory authorization in Switzerland (SwissMedic) to conduct a phase I/II trial in chronic thoracic SCI using fetal-derived NSCs (HuCNS-SC). There are important similarities and differences in the design of each of these studies. Geron’s GRNOPC1 contains hESC-derived OPCs that have demonstrated remyelinating and nerve-growth-stimulating properties leading to restoration of locomotor function in a rat model of acute contusion SCI (Keirstead et al., 2005). StemCells reported similar findings in a mouse model of spinal cord contusion injury using HuCNS-SC (Cummings et al., 2005) and demonstrated their efficacy beyond the acute injury stage (Salazar et al., 2010).