04 May 2010
Neuronal Ceroid Liposfuscinosis (NCL), often referred to as Batten disease, is a rare and fatal neurodegenerative disorder that afflicts infants and young children. NCL is caused by a deficiency of a lysosomal enzyme, and is a relatively rare disease, affecting an estimated 2 to 4 of every 100,000 babies born in the U.S. Although NCLs are classified as rare diseases, they often affect more than one child in families that carry the defective gene, and tragically, are always fatal.

Researchers at Oregon Health & Science University, Doernbecher Children's Hospital in Portland, Ore., investigated the transplantation of neural stem cells in patients with advanced stage infantile and late-infantile NCL. The results of this study, CNS Transplantation of Purified Human Neural Stem Cells in Neuronal Ceroid Lipofuscinoses: Phase I Trial, will be presented by Nathan Selden, MD, PhD, 10:15 to 10:29 am, Monday, May 3, 2010, during the 78th Annual Meeting of the American Association of Neurological Surgeons in Philadelphia. Co-authors are Daniel J. Guillaume, MD, Stephen L. Huhn, MD, Thomas K. Koch, MD, Amira Al-Uzri, MD, and Robert D. Steiner, MD.

"This is a tragic and devastating disease for children and their families, so research into finding a potential treatment - and eventually a cure - is extremely crucial," remarked Dr. Selden. The onset of the infantile form affects babies at ages 6 months to 2 years and progresses rapidly. Patients usually die before age 5, although some have survived a few years longer. The onset of late infantile form affects young children at ages 2 to 4 years and progresses fairly rapidly. Children with this form usually die between the ages of 6 and 12. The key lysosomal enzymes that are missing in the infantile and late infantile forms are Palmitoyl Protein Thioesterase 1 (PPT1) and Tripeptidyl Peptidase 1 (TPP1), respectively.

This clinical trial, the first FDA-authorized clinical trial ever undertaken in the U.S. utilizing purified human neural stem cells, was completed in January 2009. The sponsor of this study, StemCells, Inc. of Palo Alto, Calif., isolates and purifies its proprietary neural stem cells (HuCNS-SC® cells) that are naturally resident in donated brain tissue, and then expands these cells into banks from which multiple patient doses can be obtained. These tissue-derived "adult" stem cells are not genetically modified in any way nor grown with any animal feeder cells, and have thus far demonstrated a favorable safety profile both in animal studies and this first human study.

The six children who participated in this trial were comprised of four males and two females with an age range from 2 to 9 years. Two patients had the infantile form and four had the late-infantile form of NCL. The patients, all of whom were in very advanced stages of the disease, underwent bilateral intracerebral and intraventricular transplantation of HuCNS-SC cells in a single-stage surgical procedure. The low dose group received a target dose of approximately 500 million cells and the high dose group received a target dose of approximately 1 billion cells. All patients were placed on immunosuppression for 12 months after transplantation. Patients were assessed both pre- and post-transplant with a comprehensive battery of tests and magnetic resonance imaging of the brain.

The trial data demonstrated that HuCNS-SC cell transplantation in combination with immunosuppression was well tolerated by all six patients. The subjects' neurological and neuropsychological course following transplantation appeared to be consistent with the underlying disease. One patient with the infantile form died 11 months after transplantation due to the natural progression of the disease. A brain autopsy revealed no abnormalities associated with transplantation of HuCNS-SC cells, and DNA PCR testing of post-mortem brain tissue provided evidence of donor cell engraftment and survival. The remaining five patients completed the Phase I trial assessments and have been enrolled in a separate four-year, long-term follow-up study. At this time, all five patients have lived more than two years post transplant and two of the patients have lived more than three years post transplant. Preliminary interim safety results from the long-term follow-up study will also be presented by Dr. Selden.

"This Phase 1 trial was a very important first step toward finding a viable treatment and extending the life of children with this devastating disease. Initial results regarding safety associated with the transplantation of a significant cell dose are certainly promising. Further investigation of HuCNS-SC cells is warranted for infantile and late-infantile NCL, as well as for exploring this cell therapy approach for other conditions of the central nervous system," concluded Dr. Selden.