Thursday, August 30, 2007

Remember This! … Fibroblast-Neprilysin

UNTREATED Alzheimer's Brain Cells

TREATED Alzheimer's Brain Cells

Plaques comprised of amyloid-beta are the hallmark pathology of Alzheimer's disease. In this study, the scientists used an amyloid-degrading enzyme to clear these amyloid cobwebs from the brain - as illustrated in these untreated (top) versus treated (bottom) brain images. Image Credit: Harvard Photographic Services

Remember This! … Fibroblast-Neprilysin

In a report that first appeared August 27 on the Web site of the Public Library of Science, experiments centered on new methods to relieve the damaging effect of Alzheimer’s disease are showing great promise.

Simply stated, it is believed that when some humans grow older, the ability to control the build up of protein based plaques in the brain becomes reduced. These proteins create toxic clumps and tangled fibers that ultimately kill cells and interfere with the brains’ ability to recall memories and think (a situation similar to the build up of cholesterol in arteries that reduce the flow of blood).

An enzyme named Neprilysin has shown great promise in breaking down the toxic clumps of fibrous protein in the brains of mice. What has been found through these tests, and may be unique, is the method of the delivery of this enzyme to the effected portions of the brain under the toxic grip of Alzheimer’s protein-fiber goo.

Skin from the patient may actually provide the best method to first create the Neprilysin enzyme and further, through a process termed Fibroblast create a combo that can be implanted back into the patient for the desired result – a freer thinking brain.

This Fibroblast-Neprilsin combo type of tratment process has shown and may prove to have a positive benefit to the treatment of cancers, blood, muscle, and eye diseases, spinal cord injuries, stroke, Parkinson’s and Huntington diseases, and amyotrophic lateral sclerosis (Lou Gehrig’s disease).

Journey inside a cell as you follow proteins and learn about cellular interactions. This 3-D animation brings to life the inner workings of a fibroblast cell as it responds to external signals. YouTube Credit: Cold Spring Harbor Laboratory and Interactive Knowledge, Inc.

This from Harvard University Gazette Online -

Brain implants relieve Alzheimer’s damage
Toxic plaques cleared away

William J. Cromie - Harvard News Office - August 28, 2007

Genetically engineered cells implanted in mice have cleared away toxic plaques associated with Alzheimer’s disease.

The animals were sickened with a human gene that caused them to develop, at an accelerated rate, the disease that robs millions of elderly people of their memories. After receiving the doctored cells, the brain-muddling plaques melted away. If this works in humans, old age could be a much happier time of life.

Alzheimer’s involves a protein called amyloid-beta.
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“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, 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 this common and devastating disease in humans.”
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The first published report of the experiments, done by Selkoe and other researchers from Harvard-affiliated Brigham and Women’s and McLean hospitals, appeared Aug. 27 on the Web site of the Public Library of Science.

The gene delivery technique employed by the research team has been used in several other trials with animals that model human diseases, including cancers. The procedure involves removing cells from patients, making genetic changes, and then putting back the modified cells, which should treat a disease or disability.
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“Several of these potential treatments have advanced to human trials, with encouraging outcomes for patients,” says Matthew Hemming, lead author of the report and a graduate student in Selkoe’s lab.
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The Harvard team used skin cells from the animal’s own body to introduce a gene for an amyloid-busting enzyme known as neprilysin. The skin cells, also known as 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.
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Fibroblast Process - Primary chick embryo fibroblasts, expressing RFP-actin, doing their thing. Sped up approximately 300 times (each frame is 30 seconds apart in real life). YouTube Credit: cooloriginaltwic - Added: March 14, 2007

The experiments proved that the technique works, but will it work in humans?

One major obstacle, Selkoe says, is the larger size of a human brain compared to that of a mouse. That difference will require an increase of amyloid-busting activity throughout a much larger space.

One solution might involve implanting the genes and fibroblasts where they have the best access to amyloid-beta, 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.

This or some other clever maneuver that does not require surgery might eliminate the gooey plaques, but will that improve a person’s memory? And will the change be long-lasting? “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.”
Reference Here>>

(original posting from Oblate Spheroid)


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