Localized Gene Therapy Beneficial To Entire Brain In Recent Study

Philadelphia, PA (AHN) - By targeting a site in a mouse brain well connected to other areas, researchers successfully were able to deliver a beneficial gene to the entire brain. What has scientists looking to the future is that it occurred after a single injection of gene therapy. If these results in animals can be realized in people, researchers may have a new tool for gene therapy allowing health officials the ability to treat a host of rare but devastating congenital human neurological disorders.

Gene therapy is the insertion of genes into an individual's cells and tissues to treat a disease, and hereditary diseases in which a defective mutant allele is replaced with a functional one. Although the technology is still in its infancy, it has been used in the medical and scientific fields with some success and future practical applications.

Researchers from The Children's Hospital of Philadelphia and the University of Pennsylvania published their findings from their latest foray into the field in the September 12 issue of the Journal of Neuroscience.

Study leader John H. Wolfe, V.M.D., Ph.D., a neurology researcher said, "After a single injection, this technique succeeded in correcting diseased areas throughout the brain."

He goes on to say, "This may represent a new strategy for treating genetic diseases of the central nervous system."

Wolfe and his team used mice specially bred to have the neurogenetic disease mucopolysaccharidosis type VII (MPS VII) in their study. In humans, MPS VII, also called Sly syndrome, which is a rare, multisystem disease causing mental retardation and death in childhood or early adulthood.

Sly syndrome is a disorder characterized by short stature, coarsening of the facial features, clouding of the cornea, striking enlargement of the liver and spleen, skeletal abnormalities, intellectual deterioration resulting in moderately severe mental retardation, and in some cases fatal disabilities. Sadly it strikes about one in 5,000 births.

However, for Sly syndrome and most other lysosomal storage diseases, enzyme replacement, when available, is not very effective in treating the brain component of the disease.

Therefore, some strategies for treating these diseases have focused on gene therapy-delivering DNA sequences that can enter cells and produce the needed enzyme.

In the current study, Wolfe and his team focused on a particular region of the mouse brain called the ventral tegmental area (VTA).

Wolfe said, "The neural pathways carried the virus throughout the brain, where the gene produced the enzyme. The enzyme then cleaned up the storage lesions to the point that these storage lesions were indistinguishable from those found in the brains of normal mice."

One advantage of lysosomal enzymes, said Wolfe, is that cells receiving the delivered gene secrete beneficial enzymes to neighboring cells, creating a "sphere of correction." Researchers believe that if the results can be transferred to humans successfully then 2 milliliters of injected gene therapy might treat a one-year- old child.