Researchers from Harvard Medical School and the University of Pennsylvania have developed a new way to treat brain lesions in mice, and the procedure may hold promise for treating a neurodegenerative disease in humans.

Dr. Evan Y. Snyder of the Neurology and Pediatrics departments of Children's Hospital and Dr. John H. Wolfe of the School of Veterinary Medicine at the University of Pennsylvania successfully corrected disease progression in afflicted mice serving as animal models for Sly Disease, an inherited human ailment characterized by mental retardation. The fatal disease afflicts fewer than one in 100,000 humans.

Snyder and Wolfe worked with mice whose brains lacked an enzyme necessary for breaking down metabolites and waste material in cells.

Without this enzyme, called beta glucuronidase, substances called glycoaminoglycans accumulate in the brain and other tissues, where they cause neural damage. Accumulation of this waste material leads to severe brain deterioration, retardation and ultimately death.

Snyder and Wolfe reversed the disease's progression by transplanting immature healthy brain cells, called progenitor cells, into the enzyme-deficient brains of newborn mice. According to Snyder, the young cells matured into normal healthy cells, migrating and engrafting themselves in the brain as the mouse grew older.

The findings, published in the journal Nature two weeks ago, is the first report about using this technique to treat a widespread genetic disease of the central nervous system.

The unique anatomical features of the brain made conventional treatments of its lesions ineffective.

Whereas other organs can make up for missing enzymes through contact with the blood, the brain is isolated from the bloodstream by a protective sheath of impermeable capillaries: the blood-brain barrier.

The barrier blocks the entry of drugs and therapeutic molecules into the brain, preventing the correction of brain lesions.

Researchers therefore decided to inject neural progenitor cells into the brain ventricles, chambers filled with cerebrospinal fluid surrounding the brain.

Progenitor cells give rise to two types of brain cells, the neurons (nerve cells) and the glial cells (nourishing cells), which develop into specialized brain structures.

"We recognized an inherent property of immature nerve cells and exploited it," Synder said.

Since the afflicted mice are born relatively healthy, the transplant therapy was able to be used on newborns, rather than embryos.

By the time the newborn mice reached maturity, the neural progenitor cells had secreted the missing enzyme, engrafted throughout the brains and appeared as normal constituents of the central nervous system.

Mice with transplanted cells who lived over eight months, the mouse's usual lifespan, showed a dramatic absence of pathology in their brains, suggesting a permanent cure without additional abnormalities, said Wolfe.