Lysosomal Storage Disorders / NCL (Neuronal Ceroid Lipofuscinosis)
StemCells, Inc. has completed a Phase I clinical trial of HuCNS-SC® human neural stem cells in NCL, a fatal neurodegenerative disorder in children. Data from this study demonstrated the clinical safety, tolerability and viability of the cells. Learn more about our clinical trial in NCL…
In October 2010, we initiated a Phase Ib trial in NCL to further assess the safety and preliminary efficacy of HuCNS-SC cells in patients with less advanced stages of the disease than those enrolled in our first trial. In April 2011, we discontinued the Phase Ib study and shelved our NCL program due to a lack of eligible patients identified within a reasonable timeframe. However, we continue to believe in the significant therapeutic potential of our cells in NCL and possibly other lysosomal storage disorders.
In this open-label, dose-escalating study, our HuCNS-SC product candidate was transplanted into six patients with either infantile or late infantile NCL. Enrollment in the trial was limited to patients in advanced stages of the disease with significant neurological and cognitive impairment (patients whose developmental age was demonstrated to be less than two-thirds of their chronological age). The HuCNS-SC cells were directly transplanted into each patient’s brain via a neurosurgical procedure. The patients were evaluated and assessed at regular intervals using a comprehensive range of medical, neurological and neuro-psychological tests, both before transplantation to establish a baseline, and over the course of 12 months following transplantation. Following completion of the Phase I trial, the patients were automatically enrolled in a separate four-year follow-up study.
In June 2009, we reported positive results from this trial including:
- Favorable safety profile: cells, surgical procedure and immunosuppression all well tolerated
- Evidence of engraftment and long-term survival of the transplanted cells
Preclinical Proof of Concept
Published data from our preclinical studies in NCL highlights the novel neuroprotective approach that we are pursuing to treat neurodegenerative diseases, and supports our clinical development of HuCNS-SC cells.
Transplanted neural stem cells delay loss of motor coordination in INCL mice.
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When transplanted in a mouse model of infantile NCL (INCL), our human neural stem cells engraft, migrate throughout the brain and continuously secrete the missing lysosomal enzyme characteristic of NCL, which is needed to process cellular waste and keep neurons functioning and healthy. When compared with a control (non-transplanted) group, the mice that received the transplanted neural stem cells showed a statistically significant reduction in cellular waste build-up, protection of critical host neurons and delayed loss of motor function. Preclinical studies have demonstrated that our human neural stem cells also produce the enzyme missing in late infantile NCL (LINCL), thereby providing the scientific rationale for enzyme replacement via transplantation of these cells in this subtype, as well as in INCL.
Continue learning more about NCL…
