Stem-Cell Trial for Neurodegenerative Pediatric Disease to Get Under Way

The goal is a treatment for Batten disease, a rare and fatal disorder

FRIDAY, Sept. 22, 2006 (HealthDay News) -- A phase I trial to test the safety of stem-cell transplants to treat Batten disease, a rare yet fatal neurodegenerative disorder, is about to get started at Oregon Health & Science University's (OHSU) Doernbecher Children's Hospital.

A phase I trial is designed to determine the safety of a treatment and not necessarily whether it works. In this trial, six children with symptoms of the disease will be given transplants of stem cells at two different doses and followed for a year, the researchers said.

In addition to the stem cells, which will be surgically implanted into three areas of the brain, the children will be placed on drugs to help prevent rejection of the cells.

Batten disease, known as neuronal ceroid lipofuscinosis (NCL), is a rare, inherited neurodegenerative disorder. Children with the condition suffer seizures, progressive loss of motor skills, sight and mental capacity, eventually becoming blind, bedridden and unable to communicate. Currently, there's no treatment to stop or reverse the effects of the disease, which is always fatal, usually by the late teens or early 20s, according to the National Institute of Neurological Disorders and Stroke.

Symptoms typically begin between 6 months and 10 years of age. The age of onset and rate of progression depend on the inherited gene mutation. In the United States, there are approximately 200 to 600 children living with Batten disease.

"NCL patients lack an enzyme responsible for breaking down complex fat and protein compounds in the brain," lead researcher Dr. Robert D. Steiner, vice chairman of pediatric research and head of the Division of Metabolism at Doernbecher Children's Hospital, said at a press briefing Friday.

"These materials accumulate and interfere with normal cell and tissue function and ultimately cause cells to die," said Steiner, who's also a professor of pediatrics and molecular and medical genetics at Oregon Health and Science University School of Medicine.

The hope behind the new research is that the stem cells will evolve into cells that start producing the missing or defective lysosomal enzyme that causes the disease, as was the case in animal studies, he said.

Children eligible for the study have clinical symptoms of one of two types of NCL -- infantile or late infantile NCL -- and loss-of-function mutations in either the CLN1 or CLN2 gene. The children will be monitored with standardized measures of development, cognition, behavior and language for one year following transplantation, the researchers said.

This potential therapy was developed by StemCells Inc., of Palo Alto, Calif., which is sponsoring the clinical trial with its proprietary human neural stem cells, called HuCNS-SC. Theses stem cells are isolated from normal fetal brain tissue, purified, expanded and then stored in frozen cell banks until they are transplanted, the researchers said.

The trial will begin with one patient receiving the stem cells. Assuming all goes well, a second patient would receive a transplant 30 days later.

"We will begin with one patient, but we are not going to continue on with other patients until all of the safety protocols evaluated in the first patient have been met," Dr. Nathan Selden, the Campagna associate professor of pediatric neurological surgery and head of the Division of Pediatric Neurological Surgery at Doernbecher and OHSU School of Medicine, said at the briefing.

"It is our hope that this trial will provide insight into a potential treatment option for this tragic disease," Steiner said. "This trial is just the beginning in a lengthy, ongoing effort to determine a safe and effective means to improve the quality of life of those suffering from NCL," he said.

Embryonic stem-cell research in the United States has been severely restricted since Aug. 9, 2001, when President George Bush placed limits on federal funding of the field. As of that date, federal funds could only be used to study stem cell lines derived from embryos that had been destroyed before the limit was set. This has turned out to be fewer lines than originally thought, and even fewer high-quality lines.

And while some state, private and university money, including Stanford and Harvard universities, has emerged to fill the gap, it's not enough on its own, many researchers contend.

More information

The U.S. National Institute of Neurological Disorders and Stroke can tell you more about Batten disease.

SOURCES: Sept. 22, 2006, press conference with Robert D. Steiner, M.D., vice chairman of pediatric research, and head of the Division of Metabolism at Doernbecher Children's Hospital, and professor of pediatrics and molecular and medical genetics at Oregon Health and Science University School of Medicine, Portland; Nathan Selden, M.D., Ph.D., Campagna associate professor of pediatric neurological surgery, head Division of Pediatric Neurological Surgery, Doernbecher Children's Hospital, and Oregon Health and Science University School of Medicine, Portland
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