| Departments — Benchmarks | Autumn 2007 |
Disappearing Plaques Experiments by a team of scientists at Brigham and Women’s and McLean hospitals The scientists first induced the mice to develop Alzheimer’s at an accelerated rate, then implanted them with the doctored cells. The animals’ brain-muddling plaques melted away. If the research translates to humans, a debilitating disease that robs millions of elderly people of their memories could become history. The team was led by Dennis Selkoe, Vincent and Stella Coates Professor of Neurologic Diseases at HMS, and its findings were reported August 28, 2007, in PLoS Medicine. Alzheimer’s involves a protein known as amyloid-beta, which forms gooey clots or plaques in the brain. These toxic clumps, along with accessory-tangled fibers, kill brain cells and interfere with memory and thinking. The gene modification and implantation technique employed by the researchers has been used in other trials with animals that model human diseases, including cancers. The procedure involves removing cells from patients, making genetic changes, and then reintroducing the modified cells, which should treat a disease or disability. So far, this approach has produced encouraging results for cancers, spinal cord injuries, stroke, Parkinson’s and Huntington diseases, amyotrophic lateral sclerosis, and blood, muscle, and eye diseases. The Harvard team used fibroblasts from the animal’s own body to introduce a gene for an amyloid-busting enzyme known as neprilysin. These skin cells were chosen because they do not form tumors, migrate from the implantation site, or cause any detectable adverse side effects. In addition, “fail-safe” genes can be added to the fibro-blast–neprilysin combo; the genes act to eliminate the implants if something starts to go wrong. Transferable Skills “The experiment showed a robust clearance of plaques in the brains of the mice,” says Selkoe. “Such results support—and encourage—further in-vestigation of gene therapy for treatment of this common and devastating disease in humans.” Translating the successful technique to applications in humans, however, brings many hurdles. One such obstacle, Selkoe says, is the larger size of a human brain compared to that of a mouse. That difference will require the implanted genes to travel throughout a much larger space in order to affect the needed increase in amyloid-busting activity. The researchers are already devising ways to overcome difficulties. One suggestion involves implanting the genes and fibroblasts where they would have the best access to amyloid-beta—in the spinal fluid, for example—instead of trying to deliver the modified cells into a small target by injection. The amyloid-killing combo might be put into capsules that would secrete neprilysin into the blood that circulates in the brain, eliminating the need to hit an exact spot. This or some other nonsurgical maneuver might eliminate the gooey plaques, but would that improve a person’s memory? And would any change be long lasting? Further study is required, say the researchers, but there is a wealth of evidence suggesting that long-lasting improvements to memory would indeed be likely. William J. Cromie is a former staff writer for the Harvard University Gazette. Photo: © iStockphoto.com/Evgeniy Meyke |
have succeeded in ridding the brains of mice of the toxic plaques associated with Alzheimer’s disease. The cleanup tool: genetically engineered cells.
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