Clinical Trial Overview
Neuronal Ceroid Lipofuscinosis(NCL, often called Batten disease)
Neuronal ceroid Lipofuscinosis (NCL) is a rare neurodegenerative disease that affects infants and young children. The name Batten disease is derived from the British pediatrician who first described the juvenile form of NCL in 1903. The name is now often used to encompass the three forms of NCL, initially classified by age of onset (infantile, late infantile and juvenile), and now more precisely classified in terms of the specific enzyme deficiencies causing the disease. 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.
NCLs are lysosomal storage disorders brought on by inherited genetic mutations in genes that provide cells with normally secreted housekeeping lysosomal enzymes. Lack of these enzymes causes a buildup of lipofuscin (aggregates of lipids and proteins) that leads to neuronal cell loss primarily in the brain. It is believed that the non-degraded lipofuscin accumulates to the point where it interferes with normal cellular and tissue function, which leads to the manifestations of the disease.
In two sub-types of NCL - infantile and late infantile - genes have been identified that are either defective or missing altogether. These genes are CLN1, which codes for the enzyme palmitoyl-protein thioesterase 1 (PPT1), and CLN2, which codes for the enzyme tripeptidyl peptidase I (TPP-I). Replacement of defective enzymes or genes is the objective of research into treatments for Batten disease and other lysosomal storage diseases.
Human Central Nervous System Stem Cells
StemCells' human central nervous system stem cells (HuCNS-SC?) are a cell therapy product consisting of neural cells prepared under controlled conditions. Neural stem cells are isolated from the human fetal brain, purified, expanded and then stored and frozen in cell banks until they are transplanted as HuCNS-SC doses. Preclinical data has shown that HuCNS-SC survive transplantation, migrate to different regions of the brain and become specialized cells normally found in that region. HuCNS-SC have also been shown to produce both the PPT1 and TPP-I enzymes. In preclinical models of PPT1 deficiency, the corresponding enzyme activity increases with time after transplantation. Thus, placement of HuCNS-SC in appropriate places in the brain has the prospect of replacing missing enzymes.
Phase I Clinical Trial of Human Central Nervous System Stem Cells
StemCells has initiated a Phase I trial to investigate the safety and preliminary efficacy of HuCNS-SC as a treatment of infantile and late-infantile NCL. HuCNS-SC will be transplanted into the brain through a surgical procedure performed by a pediatric neurosurgeon. The trial is an open label study of two dose levels. The primary objective of the trial will be to measure the safety of HuCNS-SC. The trial will also evaluate HuCNS-SC's ability to affect the progression of the disease. The primary evaluation will be at one year post HuCNS-SC transplantation and patients will be asked to permit monitoring to be continued for at least a five year period after transplantation.
Eligibility for Phase I Clinical Trial
Children who have loss of function mutations in either the CLN1 or CLN2 genes may be eligible for the study. Potential patients will be tested for eligibility and evaluated for baseline disease status. If you are not sure whether your child has either the CLN1 or CLN2 mutation, your doctor can advise you on having genetic testing performed. The following diagnostic laboratory does this testing:
Neurogenetics DNA Diagnostic Lab
149 13th Street, Rm #6311
Charlestown , MA 02129
Tel: (617) 726-5721
Fax: (617) 724-9620
http://www.massgeneral.org/neuroDNAlab
Further Information
StemCells has received clearance from the U.S. Food and Drug Administration (FDA) to initiate the Phase I clinical study and has also received approval from the Institutional Review Board (IRB) at the Oregon Health & Science University to begin the trial at OHSU Doernbecher Children?s Hospital in Portland, Oregon.
If you are a patient, family member or friend of a patient with NCL/Batten disease, and would like further information on the study, please call 650-475-3123 for more information. If you would like to be notified when more information becomes available or when StemCells, Inc. begins a new clinical trial related to this or another disease, please click here to add yourself to our database http://www.stemcellsinc.com/clinicaltrials/template.php
Neuronal Ceroid Lipofuscinosis(NCL, often called Batten disease)
Neuronal ceroid Lipofuscinosis (NCL) is a rare neurodegenerative disease that affects infants and young children. The name Batten disease is derived from the British pediatrician who first described the juvenile form of NCL in 1903. The name is now often used to encompass the three forms of NCL, initially classified by age of onset (infantile, late infantile and juvenile), and now more precisely classified in terms of the specific enzyme deficiencies causing the disease. 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.
NCLs are lysosomal storage disorders brought on by inherited genetic mutations in genes that provide cells with normally secreted housekeeping lysosomal enzymes. Lack of these enzymes causes a buildup of lipofuscin (aggregates of lipids and proteins) that leads to neuronal cell loss primarily in the brain. It is believed that the non-degraded lipofuscin accumulates to the point where it interferes with normal cellular and tissue function, which leads to the manifestations of the disease.
In two sub-types of NCL - infantile and late infantile - genes have been identified that are either defective or missing altogether. These genes are CLN1, which codes for the enzyme palmitoyl-protein thioesterase 1 (PPT1), and CLN2, which codes for the enzyme tripeptidyl peptidase I (TPP-I). Replacement of defective enzymes or genes is the objective of research into treatments for Batten disease and other lysosomal storage diseases.
Human Central Nervous System Stem Cells
StemCells' human central nervous system stem cells (HuCNS-SC?) are a cell therapy product consisting of neural cells prepared under controlled conditions. Neural stem cells are isolated from the human fetal brain, purified, expanded and then stored and frozen in cell banks until they are transplanted as HuCNS-SC doses. Preclinical data has shown that HuCNS-SC survive transplantation, migrate to different regions of the brain and become specialized cells normally found in that region. HuCNS-SC have also been shown to produce both the PPT1 and TPP-I enzymes. In preclinical models of PPT1 deficiency, the corresponding enzyme activity increases with time after transplantation. Thus, placement of HuCNS-SC in appropriate places in the brain has the prospect of replacing missing enzymes.
Phase I Clinical Trial of Human Central Nervous System Stem Cells
StemCells has initiated a Phase I trial to investigate the safety and preliminary efficacy of HuCNS-SC as a treatment of infantile and late-infantile NCL. HuCNS-SC will be transplanted into the brain through a surgical procedure performed by a pediatric neurosurgeon. The trial is an open label study of two dose levels. The primary objective of the trial will be to measure the safety of HuCNS-SC. The trial will also evaluate HuCNS-SC's ability to affect the progression of the disease. The primary evaluation will be at one year post HuCNS-SC transplantation and patients will be asked to permit monitoring to be continued for at least a five year period after transplantation.
Eligibility for Phase I Clinical Trial
Children who have loss of function mutations in either the CLN1 or CLN2 genes may be eligible for the study. Potential patients will be tested for eligibility and evaluated for baseline disease status. If you are not sure whether your child has either the CLN1 or CLN2 mutation, your doctor can advise you on having genetic testing performed. The following diagnostic laboratory does this testing:
Neurogenetics DNA Diagnostic Lab
149 13th Street, Rm #6311
Charlestown , MA 02129
Tel: (617) 726-5721
Fax: (617) 724-9620
http://www.massgeneral.org/neuroDNAlab
Further Information
StemCells has received clearance from the U.S. Food and Drug Administration (FDA) to initiate the Phase I clinical study and has also received approval from the Institutional Review Board (IRB) at the Oregon Health & Science University to begin the trial at OHSU Doernbecher Children?s Hospital in Portland, Oregon.
If you are a patient, family member or friend of a patient with NCL/Batten disease, and would like further information on the study, please call 650-475-3123 for more information. If you would like to be notified when more information becomes available or when StemCells, Inc. begins a new clinical trial related to this or another disease, please click here to add yourself to our database http://www.stemcellsinc.com/clinicaltrials/template.php