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Dec. 21 - Brain Implants Relieve Alzheimer’s Damage

Genetically engineered cells implanted in mice have cleared away toxic plaques associated with Alzheimer’s disease. The mice were given a human gene that caused them to develop Alzheimer’s at an accelerated rate. After receiving the doctored cells, the plaques melted away. Alzheimer’s involves the protein amyloid-beta, which makes up clots or plaques that form in the brain, kill brain cells and interfere with memory and thinking.

“Delivery of genes that led to production of an enzyme that breaks up amyloid showed robust clearance of plaques in the brains of the mice,” notes Dennis Selkoe, MD, Vincent and Stella Coates professor of neurologic diseases at Harvard Medical School. “These results support and encourage further investigation of gene therapy for treatment of (Alzheimer’s) in humans.”

The experiments were done by Selkoe and other researchers from Harvard-affiliated Brigham and Women’s and McLean hospitals. The gene-delivery technique has been used in several other trials with animals that model human diseases. It involves removing cells from patients, making genetic changes, and then replacing them. So far, the approach has produced encouraging results for cancers; blood, muscle, and eye diseases; spinal cord injuries; stroke; Parkinson’s and Huntington diseases, and ALS. “Several of these potential treatments have advanced to human trials, with encouraging outcomes for patients,” says Matthew Hemming, PhD, lead author.

Researchers used skin cells from the animal’s body to introduce a gene for an amyloid-busting enzyme called neprilysin. The cells, or fibroblasts, “do not form tumors or move from the implantation site,” Hemming notes. “They cause no detectable adverse side effects and can easily be taken from a patient’s skin.” In addition, other genes can be added to the fibroblast-neprilysin combo, which will eliminate the implants if something starts to go wrong. … The gene that removed the amyloid-beta may not only prevent brain cells from dying, but will also remove the toxic protein that drives the disease progression.” Will the technique work in humans? One major obstacle, Selkoe says, is the obvious size of a human brain compared to a mouse. The difference will require an increase of amyloid dissolution throughout a much larger space.

One solution might involve implanting the genes and fibroblasts where they have the best access to amyloid, in the spinal fluid for example, instead of trying to inject them into a small target. The amyloid-killing combo might be put into capsules that would secrete neprilysin into the blood circulating in the brain, eliminating the need to hit an exact spot. “Further work is needed to determine if reducing the plaque burden has cognitive benefits over a long period,” notes Hemming, “but there’s a wealth of evidence arguing that it will.”

Source: Harvard News Office

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