About 45 lysosomal storage diseases are known, each caused by a genetic defect that knocks out an enzyme needed for normal function of lysosomes, cellular organelles that digest proteins, fats, carbohydrates and nucleic acids. When a lysosomal enzyme is missing, the material it normally breaks down builds up to harmful levels inside cells. The enzyme missing in Twitcher mice and Krabb sufferers is responsible for getting rid of a particular kind of fat common in nerve cells.
"Lysosomal storage diseases are some of the most devastating diseases around," Sands says. "Children appear normal at birth, but slowly deteriorate. Between 5 and 10 years old they are often deaf, blind, mentally retarded and confined to wheelchairs, and the disease just marches on. The infantile form of Krabb disease is usually fatal by age 2."
Sands and his colleagues previously showed they could increase enzyme levels in the brains of Twitcher mice to as much as 25 times normal levels by injecting directly into the brain viral vectors that held the gene for the missing enzyme.
This procedure is a form of gene therapy, a technique for correcting defective genes responsible for disease development. A similar injection procedure is currently being used in a Phase I clinical trial at Cornell University as a treatment for children with late infantile Batten disease, another lysosomal storage disease. Unfortunately, gene therapy alone didn't fully correct the disease in Twitcher mice in Sands' early experiments, and it only slightly increased their lifespan. On the other hand, decades of prior research with Twitcher mice had shown that under extreme treatment conditions bone marrow transplantation could extend the lives of these mice to an average of about 80 days (untreated Twitcher mice live to approximately 38 days).
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
9-Jan-2007