In what may lead to a new strategy to treat a host of rare but devastating congenital human neurological disorders like Tay-Sachs disease, researchers from The Children's Hospital of Philadelphia and the University of Pennsylvania have achieved success in delivering a beneficial gene to the entire brain of a mouse after one injection of gene therapy.
"After a single injection, this technique succeeded in correcting diseased areas throughout the brain," said Dr. John H. Wolfe, a neurology researcher at The Children's Hospital of Philadelphia and a professor of pathology and medical genetics at the Penn School of Veterinary Medicine.
"This may represent a new strategy for treating genetic diseases of the central nervous system," added Dr. Wolfe, who is also the leader in the study published in the Journal of Neuroscience.
The mice used in the study were specially bred to have the neurogenetic disease mucopolysaccharidosis type VII (MPS VII), a rare multi-system disease that causes mental retardation and death in childhood or early adulthood, which is also known as Sly syndrome.
Dr. Wolfe revealed that he targeted a particular region of the mouse brain called the ventral tegmental area (VTA), which has numerous connections with the rest of the brain. He used a neutralized virus called adeno-associated virus (AAV) as a vector, the delivery vehicle for the gene that carries coded instructions to produce the desired enzyme.
"We found that one subtype of AAV was particularly effective for transporting the gene. 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," said Wolfe.
He further said that one of the advantages of lysosomal enzymes was that cells receiving the delivered gene secrete beneficial enzymes to neighbouring cells, creating a "sphere of correction". Dr. Wolfe said that the level of correction resulting from a single injection was "unprecedented".
According to him, two millilitres of injected gene therapy might treat a one-year-old child if the animal results could be successfully extrapolated to humans. He, however, has admitted that it may take several years before direct human treatments may be available.
He also revealed that he was planning further studies to determine whether his technique would be effective in animals larger than mice.