Laboratory
BSRB 346
615 Charles E. Young Drive South
Los Angeles, CA 90095
Office
BSRB 350B
615 Charles E Young Drive South
Los Angeles, CA 90095
Our interests have long been the cause, consequences and treatment of human genetic diseases due to deficiency of lysosomal enzymes. The disease currently under investigation is the Sanfilippo syndrome type B (MPS III B). It is caused by mutation in the NAGLU gene, with resulting deficiency of the lysosomal enzyme alpha-N-acetyl-glucosaminidase and accumulation of its substrate (heparan sulfate). The disease manifests itself in childhood by severe mental retardation and intractable behavioral problems. The neurologic deterioration progresses to dementia, with death usually in the second decade. We use a mouse knockout model (Naglu -/-) in order to study the pathophysiology of the disease and to develop therapy. Because of the special cell biology of lysosomal enzymes, which can be taken up by receptor-mediated endocytosis, exogenous administration of the enzyme could theoretically cure the disease. Unfortunately, the blood-brain barrier (BBB) prevents the therapeutic enzyme from reaching the brain. Part of our current research is to develop a novel technology to get lysosomal enzymes across the BBB. We also study changes in gene and protein expression in some specific parts of the brain, in which there is accumulation of certain lipids and proteins which seem unrelated biochemically to each other or to the primary defect. We try to understand the cause and consequences of these accumulations. Although they are secondary defects, they may be relevant to the pathophysiology of the dieease and may have represent targets for pharmacologic intervention.
Our interests have long been the cause, consequences and treatment of human genetic diseases due to deficiency of lysosomal enzymes. The disease currently under investigation is the Sanfilippo syndrome type B (MPS III B). It is caused by mutation in the NAGLU gene, with resulting deficiency of the lysosomal enzyme alpha-N-acetyl-glucosaminidase and accumulation of its substrate (heparan sulfate). The disease manifests itself in childhood by severe mental retardation and intractable behavioral problems. The neurologic deterioration progresses to dementia, with death usually in the second decade. We use a mouse knockout model (Naglu -/-) in order to study the pathophysiology of the disease and to develop therapy. Because of the special cell biology of lysosomal enzymes, which can be taken up by receptor-mediated endocytosis, exogenous administration of the enzyme could theoretically cure the disease. Unfortunately, the blood-brain barrier (BBB) prevents the therapeutic enzyme from reaching the brain. Part of our current research is to develop a novel technology to get lysosomal enzymes across the BBB. We also study changes in gene and protein expression in some specific parts of the brain, in which there is accumulation of certain lipids and proteins which seem unrelated biochemically to each other or to the primary defect. We try to understand the cause and consequences of these accumulations. Although they are secondary defects, they may be relevant to the pathophysiology of the dieease and may have represent targets for pharmacologic intervention.
Born in France, Elizabeth Neufeld immigrated to the United States in 1940. She obtained a BS from Queens College, New York and a Ph.D. from the University of California Berkeley. After postdoctoral training in, she moved to the NIH in Bethesda, MD, where she began her studies of a rare group of genetic diseases. She moved back to California in 1984 as Chair of the Department of Biological Chemistry - a position that she occupied till 2004.
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