, 2011). Another CNS regenerative/cell check details replacement strategy utilizes drugs or cytokines, rather than stem cell transplantation, to stimulate the patient’s endogenous NSCs. Stem Cell Therapeutics, for example, has treated patients with acute ischemic stroke (clinicaltrials.gov NCT00362414) with a 9 day drug regimen of Beta-hCG plus Erythropoietin (NTx-265). This drug combination is postulated to stimulate the patient’s

own resident NSCs to reduce brain damage and promote regenerative processes in the ischemic brain region. A phase IIb clinical trial was reported in May 2010 to have failed to show efficacy due to unexplained high-level response in the placebo group as well as the

experimental group. Stem cells may also be used to deliver therapeutic molecules, in some cases being modified prior to transplantation for use as a delivery vehicle to target sites of pathology (see Table 3). The types of molecules delivered include (1) neurotrophic factors and cytokines that can enhance regeneration, reduce cell damage and scarring, and promote process outgrowth and connectivity, (2) enzymes that can replace lost or mutated processes, and (3) chemotherapeutic agents for novel tumor treatments (Figure 4). The first FDA-authorized IND using prospectively purified, ex vivo-expanded NSCs derived from donated fetal human brain (HuCNS-SC) was sponsored by StemCells for enzyme replacement in the two infantile forms of (NCL; Batten’s

Disease), Buparlisib mouse a rare and fatal lysosomal storage disease in which a genetic defect leads to abnormal accumulations in lysosomes, neuronal dysfunction, and loss. The preclinical rationale Adenylyl cyclase was established in the immunodeficient PPT1 knockout mouse that exhibits key hallmarks of the human disease (Gupta et al., 2001). HuCNS-SC transplanted into the mouse brain migrated widely and produced the deficient PPT1 enzyme, leading to reduced stored material, preservation of hippocampal and cortical neurons, and a delay in motor coordination loss (Tamaki et al., 2009). The NCL phase I open-label study enrolled six pediatric patients with severe infantile and late-infantile NCL in a dose escalation design: testing a total dose of 500 million cells in the first three patients and one billion in the next three patients. The surgery, which involved multiple bilateral HuCNS-SC transplants into the brain in a single-stage procedure, was well tolerated and was followed by 12 months of immunosuppression. Postmortem evidence of donor cell survival was obtained in one subject who expired from the underlying disease 11 months after transplant. This phase I study, reported in June 2009, was the first to show human safety data with a NSC product (Steiner et al., 2009).