Skip to comments.Oregon Health & Science University first to try stem-cell shots for child disease
Posted on 03/10/2006 10:18:42 PM PST by Coleus
Oregon Health & Science University will be the first, and maybe only, hospital to give a risky experimental stem-cell transplant to children dying of a rare nerve-destroying disease. In the coming months, as many as six children with Batten disease will travel to OHSU for injections of neural stem cells, primitive cells that can form new brain and nerve cells.
The stem cells are taken from human fetuses, with their mothers' agreement, and processed and purified by a California company, StemCells Inc. At OHSU, a surgeon will inject the stem cells into eight areas of each child's brain. The theory is that the stem cells will take root and grow in the brain, making enzymes missing in children with the two forms of Batten disease being studied, said Dr. Robert Steiner, the principal investigator at OHSU's Doernbecher Children's Hospital.
The roughly one in 100,000 children with these incurable diseases can't clear toxins that gather in their cells. They generally lose their vision, develop seizures and dementia, and die before their teens. That grim outlook helped persuade OHSU's scientists to join the trial, even though its benefits are unclear. No one has ever put these stem cells in a person, and the procedure may not help anyone. This early-stage human trial aims mostly to see whether the treatment is safe, as opposed to effective.
"These cells have never been transplanted into a human being before, nor anything like them," said Martin McGlynn, StemCells Inc. president and chief executive. "These are uncharted waters." In tests on mice with a Batten-like disease, the stem cells grew and helped make the missing enzyme, limiting nerve damage and extending the mice's lives, McGlynn said. The chance that people could see similar results weighs against the trial's risks, which include bleeding in the brain and infection.
McGlynn said other health centers are deciding whether to join the trial, but he would not name them. The company withdrew an application from Stanford University after its board asked for more information on possible benefits, which McGlynn said would take too much time to provide. For parents of children with Batten disease, the start of this trial "is like coming out of the darkness into brilliant sunlight," said Marcus Kerner, an assistant U.S. attorney in Trabuco Canyon, Calif. Kerner's 6-year-old son, Daniel, can't speak or walk, though he can see and think, his father said. The family has applied to join the trial, and Kerner hopes to travel to Oregon for Daniel's treatment.
"Despite this being phase one safety research, we believe this is going to be one of the most profound medical breakthroughs in history, and we believe it's going to save his life," he said. Doctors stress that there's no way to know whether the stem cells will help until the trial is over. But the hope that the trial may help create a new kind of treatment inspires them to move ahead, said Dr. Nathan Selden, the Campagna Associate Professor of pediatric neurological surgery at OHSU.
"We constantly face diseases for which there is no really good treatment," Selden said. "And we live for the days when we can see that change."
"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.
Both hospitals are excellent.
My daughter is about to finish her second term
as a third year PharmD student at OHSU.
She will understand this. ;o)
Thank you for the post.
What does this mean? Is this an 'in utero' procedure? It almost sounds like it because they use the word 'mother'. Or, are they talking about aborted fetuses that the 'mothers' are allowing to be used for stem-cell harvesting, and then the stem cells are processed as described and then used as 'medicine' for other children.
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.
I'd like to know how they are doing this... I assume you have to kill the fetus to harvest his/her stem cells?? Am I correct?
Sure looks like the "fetus" has expired and is acting as an organ donor...especially since no mention is made of the effect of removing stem cells from the fetus.
I thought we weren't going to allow this kind of research?
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I'd like to know how they are doing this... I assume you have to kill the fetus to harvest his/her stem cells?? Am I correct? >>>
I'm not too sure. I was thinking of that while I was posting it, I certainly hope that's not true.
Of course they are obtaining the neural cells from aborted (or about to be aborted) babies.
As soon as they see any significant success in using "reclaimed" fetal tissues, especially if they develop any life prolonging treatments for general use, i.e. immortality, then it won't be very long before abortions become free and eventually they will begin to pay women for the right to harvest fetal tissue.
Come, Lord Jesus and save the innocent.
**Come, Lord Jesus and save the innocent.**
you couldnt have been more wrong you see!
defamation is also a sin. not important that you dont know about the matter