"NCL is a heartbreaking and devastating diagnosis for children and their families," said Robert D. Steiner, M.D., F.A.A.P., F.A.C.M.G., vice chairman of pediatric research, head of the Division of Metabolism and the study's principal investigator at Doernbecher Children's Hospital, OHSU. Steiner also is an associate professor of pediatrics, and molecular and medical genetics in the OHSU School of Medicine. "While the preclinical research in the laboratory and in animals is promising, it is important to note that this is a safety trial and, to our knowledge, purified neural stem cell transplantation has never been done before. It is our hope that stem cells will provide an important therapeutic advance for these children who have no other viable options."
NCL is caused by mutations or changes in the genes responsible for teaching the body how to make certain enzymes. Without these enzymes or proteins, material builds up inside brain neurons and other brain cells, causing a rapidly progressive decline in mental and motor function, blindness, seizures and early death. This study addresses two forms of NCL: infantile neuronal ceroid lipofuscinosis (INCL) and late-infantile neuronal ceroid lipofuscinosis (LINCL). Tragically, children with INCL typically die before age 5 and those with LINCL typically do not live past age 12.
"If delivering stem cells directly into the human brain is safe and effective, it will, in my opinion, be a major step forward in the efforts of scientists and clinicians around the country to find new treatments with the potential to help tens of thousands of patients with degenerative brain diseases," said co-investigator Nathan Selden, M.D., Ph.D., F.A.C.S., F.A.A.P. "I am proud that Doernbecher Children's Hospital will be part of this effort." Selden is Campagna Associate Professor of Pediatric Neurological Surgery and head of the Division of Pediatric Neurological Surgery, Doernbecher and OHSU School of Medicine.
Up to six children from Oregon or around the country will undergo HuCNS-SC transplantation at Doernbecher. Previous studies of mice that are missing one of the enzymes that causes NCL have shown HuCNS-SC increases the amount of the missing enzyme, reduces the amount of abnormal material in the brain and prevents the death of some brain cells. No major side effects have been reported in animals.
StemCells, Inc. received clearance from the U.S. Food and Drug Administration to initiate a Phase 1 clinical trial of HuCNS-SC in October 2005. The company believes this will be the first trial using a purified composition of neural stem cells as a potential therapeutic agent in humans.
StemCells' human central nervous system stem cells, HuCNS-SC, are a somatic cell therapy product consisting of neural cells prepared under controlled conditions. Neural stem cells, a rare subset of brain cells, are isolated from the human fetal brain, purified, propagated, and tested; they are then frozen in cell banks from which HuCNS-SC doses can be prepared.
ABOUT THE CLINICAL TRIAL
The Phase I trial will not enroll participants with a third form of the disease, juvenile NCL. In addition to measuring the safety of HuCNS-SC, the trial may provide initial data on the ability of HuCNS-SC to affect the progression of the disease. Potential participants will be tested for eligibility and then evaluated for baseline disease status prior to transplantation of HuCNS-SC. Children enrolled in the study will be evaluated with standardized measures of development, cognition, behavior and language for one year following HuCNS-SC transplantation. StemCells, Inc. is committed to following the effects of this therapy long-term, so subjects will also be asked to commit to a four-year follow-up study.
Stephen L. Huhn, M.D., F.A.C.S., F.A.A.P., chief of pediatric neurosurgery at Stanford Medical School; and Gregory M. Enns, M.B., Ch.B., assistant professor and director, Biochemical Genetics Program, Division of Medical Genetics, also of Stanford Medical School, played a major role in the pre-clinical research and design of the protocol for this clinical trial.
ABOUT NCL (INCL AND LNCL)
Infantile and late-infantile NCL are brought on by inherited mutations in the CLN1 gene, which codes for palmitoyl-protein thioesterase 1 (PPT1) or in the CLN2 gene, which codes for tripeptidyl peptidase I (TPP-I). The consequence of these mutations is either a defective or a missing enzyme that leads to accumulation of lipofuscin-like fluorescent inclusions in various cell types. It is thought that these non-degraded lysosomal substrates accumulate to the point where they interfere with normal cellular and tissue function and ultimately lead to the pathological manifestations of the disease. One way to approach treatment of the disease is to provide the brain with a replacement source of functional enzyme that can be taken up by the enzyme-deficient cells.
OHSU is Oregon's only health and research university. As part of its multifaceted public mission, OHSU strives for excellence in scholarship, research, clinical practice and community service. OHSU includes four schools, two hospitals, numerous primary and specialty care clinics, multiple research centers and institutes and dozens of community service programs. OHSU's fundamental purpose is to improve the well-being of people in Oregon and beyond.
ABOUT STEMCELLS, INC.
StemCells, Inc. is a development stage biotechnology company focused on the discovery, development and commercialization of stem cell-based therapies to treat diseases of the nervous system, liver and pancreas. The Company's stem cell programs seek to repair or repopulate neural or other tissue that has been damaged or lost as a result of disease or injury. StemCells is the first company to directly identify and isolate human neural stem cells from normal brain tissue. These stem cells are expandable into cell banks for therapeutic use, which demonstrates the feasibility of using normal, non-genetically modified cells as cell-based therapies. StemCells is a publicly traded company solely focused on stem cell research and development and has approximately 40 U.S. and 100 non-U.S. patents, as well as more than 100 patent applications pending worldwide. Further information about the company is available on its web site at: www.stemcellsinc.com.