Stem Cell Research
Human Neural Stem Cells Transplantation to Help Children with Batten Disease,under trial
By Akanksha, Pharmacology Correspondent
Feb 2, 2005, 10:24

Batten disease is a rare, fatal genetic disorder that affects the central nervous system of children.If approved by the FDA, this would mark the first-ever FDA-approved clinical trial to use a purified composition of human neural stem cells as the potential therapeutic agent.

StemCells Inc.,today announced that it has been in communication with the U.S. Food and Drug Administration (FDA) regarding the filing of the Company's first Investigational New Drug (IND)application.The filing, announced on January 4,2005,is for a Phase I clinical trial of StemCells' proprietary neural cell therapy product-HuCNS-in Batten disease.

“This is truly a significant milestone, not only for StemCells,Inc.,but also for all scientists who have been seeking to evaluate possible therapies for neural and neurodegenerative diseases,” said Martin McGlynn, chief executive officer of StemCells, Inc.

He added,“Our pre-clinical research has shown great promise and this filing is an essential step in discovering how to translate those pre-clinical results into treatment of human victims of terrible disorders like Batten disease and other neurodegenerative lysosomal storage diseases.It is only a first step, though–this is a Phase I,or safety, trial, from which we hope to learn about the behavior of the cells when they are transplanted into a human recipient.There will be many other steps to take before we arrive.But it is our hope that transplantation of human neural stem cells could prove to be a platform technology for a wide range of conditions for which there is now no reliable and effective treatment.”

“We are looking forward to working with the scientists at StemCells in this historic clinical trial,” said Dr. Huhn, at the Stanford University School of Medicine. “We are exploring new territory, which dictates that we proceed with due caution.I believe, however, that our path has been determined by rigorous research and a well-designed protocol.Physicians have been essentially helpless to assist children suffering from Batten’s, and all of us involved in this trial are hoping it will lead to a future in which we will have an efficient treatment, or even a cure.As a pediatric neurosurgeon, I am particularly excited about this avenue of research.”

The proposed Phase I trial is designed to investigate the safety of HuCNS-SC in the treatment of infantile and late-infantile neuronal ceroid lipofuscinosis (NCL),the most severe forms of a group of disorders commonly referred to as Batten disease.

The trial will be an open label study of two dose levels involving three subjects in each of two cohorts.The primary objective of the trial will be to measure the safety of HuCNS-SC, however, the trial will also evaluate HuCNS-SC’s ability to affect the progression of the disease.The patient/subject evaluation will be up to one year post HuCNS-SC transplantation. Candidates from anywhere in the world will be referred by their primary physicians to the Co-principal Investigators at LPCH/SUMC. Potential patients will be tested for eligibility and then evaluated for baseline disease status prior to transplantation.

Batten disease is named after the British pediatrician who first described the juvenile form of NCL in 1903. It is also known as Spielmeyer-Vogt-Sjogren-Batten disease.The name is now commonly used to encompass all three forms of NCL.

The forms of NCL are classified by age of onset (infantile, late infantile and juvenile) but are more precisely classifiable in terms of the specific enzyme causing the disease.They all have the same basic cause–lack of a lysosomal enzyme–and similar progression and outcome, but are all genetically different.Children with Batten disease suffer seizures, progressive loss of motor skills, sight and mental capacity, eventually becoming blind, bedridden and unable to communicate.Today,Batten disease is always fatal.

In two sub-types of the NCLs – infantile and late infantile or, more technically,CLN1 and CLN2–normally secreted housekeeping lysosomal enzymes are either defective or missing altogether, as a result of gene mutations.Lack of either enzyme causes a buildup of lipofuscin (aggregates of lipids and proteins) primarily in the brain and leads to neuronal cell loss.

These lysosomal storage disorders are brought on by inherited genetic mutations in CLN1 gene,which codes for palmitoyl-protein thioesterase 1(PPT1) and in the CLN2 gene, which codes for tripeptidyl peptidase I (TPP-I).

The consequence of these mutations is the accumulation of lipofuscin-like fluorescent inclusions in various cell types that eventually lead to cell degeneration.

In the proposed clinical trial, HuCNS-SC will be transplanted in the CLN1 and CLN2 patients in part to determine if the transplanted cells secrete the missing lysosomal enzymes in the brains of affected individuals.

HuCNS-SC have been shown to produce both PPT1 and TPP-I enzymes, providing a scientific justification for enzyme replacement and cellular rescue in this indication.In preclinical models of PPT1 deficiency, the corresponding enzyme activity increases with time after transplantation.

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