Brain implants relieve Alzheimer's damage
Toxic plaques cleared away
William J. Cromie
Harvard News Office
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, which makes up
gooey clots or plaques that form in the brain. These toxic clumps,
along with accessory tangled fibers, kill brain cells and interfere
with memory and thinking. The situation has been compared to a build-
up of cholesterol in coronary arteries.
"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."
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. So far, this
approach has produced encouraging results for cancers, blood, muscle,
and eye diseases, spinal cord injuries, stroke, Parkinson's and
Huntington diseases, and amyotrophic lateral sclerosis (Lou Gehrig's
disease). "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.
Another way to do gene therapy involves using a virus to carry the
curative gene to target cells. However, two people have died and
three contracted leukemia in experiments using this method. The
drawback of using viruses this way is that the added gene often mixes
with the patient's genome in ways that can lead to unwanted side
effects, including cancer and, possibly, death.
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-neprilys
something starts to go wrong.
Will it work in humans?
This method worked well in the Alzheimer's experiments. "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,
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."
Brain implants relieve Alzheimer's damage
Toxic plaques cleared away
William J. Cromie
Harvard News Office
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, which makes up
gooey clots or plaques that form in the brain. These toxic clumps,
along with accessory tangled fibers, kill brain cells and interfere
with memory and thinking. The situation has been compared to a build-
up of cholesterol in coronary arteries.
"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."
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. So far, this
approach has produced encouraging results for cancers, blood, muscle,
and eye diseases, spinal cord injuries, stroke, Parkinson's and
Huntington diseases, and amyotrophic lateral sclerosis (Lou Gehrig's
disease). "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.
Another way to do gene therapy involves using a virus to carry the
curative gene to target cells. However, two people have died and
three contracted leukemia in experiments using this method. The
drawback of using viruses this way is that the added gene often mixes
with the patient's genome in ways that can lead to unwanted side
effects, including cancer and, possibly, death.
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-neprilys
something starts to go wrong.
Will it work in humans?
This method worked well in the Alzheimer's experiments. "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,
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."
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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