Feb. 10--Inside a research laboratory on the north campus of the University of
New Mexico, genetically modified mice with Alzheimer's disease, who have been
treated with drugs and imaged with nanoparticles, are finding their way home
Although it's a long journey from mice to humans, the breakthrough discovery
could one day help people who suffer the disease's memory losses and cognitive
decline, robbing them of the pleasures of daily living and eventually stealing
Alzheimer's affects more than 5.3 million Americans and is expected to triple by
2050, unless treatment is discovered to slow, stop or prevent the disease, says
researcher Laurel O. Sillerud, a biophysicist at UNM.
"Mice love to swim," Sillerud says of testing the mice, who have cheated
In the tests, mice are put in a milky bath on a platform. The water is opaque so
the mice, who have been trained for the task, must rely on memory to find the
platform and get out of the water, he says.
Without Alzheimer's, mice can find the platform again in five seconds.
With Alzheimer's and without recall, mice cannot find the platform and get out
of the water, swimming aimlessly around and around, much like people with
Alzheimer's disease wander.
Mice treated with drugs and imaged with nanoparticles or SPIONS,
superparamagnetic iron oxide nanoparticles that can detect their disease
progression and remission through magnetic resonance, can find the platform in
10 to 15 seconds, he says.
Lisa Kuuttila, CEO and chief economic development officer at STC.UNM, UNM's
technology transfer and economic development organization, says the research is
"This innovation overcomes a major hurdle in Alzheimer's disease treatment as
there is currently no comparable method for clinical imaging of Alzheimer's
disease progression and regression. It's possible that this innovation can be
moved from the lab to the clinic relatively quickly as it is non-toxic,
non-radioactive and noninvasive."
But without more funding and additional researchers, Sillerud doesn't know if or
when people could be treated with the nanoparticles: "We have a tiger by the
tail. With support for this, we could revolutionize Alzheimer's diagnosis and
Sillerud says he didn't start out to research Alzheimer's, until his wife, Anna
Champlin, chief of interventional radiology at University Hospital, was
diagnosed with the disease when she was 50 years old. Nine years later in 2009,
she passed away.
A pioneer in nanotechnology, Sillerud has developed similar research for cancer
and was instrumental in founding nanoMR in Albuquerque. The company uses
immunomagnetic technology to identify and target blood pathogens, including
bacteria and cancer cells, with biologic identifiers and magnetic resonance.
Although the exact origin and nature of Alzheimer's disease is unknown, a
neuroinflammatory response against an abnormal formation of plaques and tangles
containing the fibrous protein amyloid-B is associated with the disease, he
In the past 12 years of his research, Sillerud and his team used the
nanoparticles and magnetic resonance imaging to detect that disease process.
The nanoparticle is an iron oxide molecule coated in antibodies that recognize
the plaques and tangles and inflammation that surrounds them in the brain: After
the plaques and inflammation are identified, the iron oxide molecules amplify
the signal from the plaques so they are more effectively detected by MRI, he
"The first step was measuring the intensity of the disease," he says. "Using
SPIONS enhances the appearance of the plaques. The nanoparticles enhance our
ability to monitor both processes. We are the first to demonstrate the targeting
of inflammation with nanoparticles."
Few other imaging techniques can measure the Alzheimer's disease process in the
brains of living creatures, he says. Although injectable agents can allow
positron emission tomography (PET) to identify them, it is about 10 times more
expensive than using MRI, he says.
"Since clinical MRI systems ... are widely available now, this opens the
possibility that quantitative AD (Alzheimer's disease) research that is
noninvasive and non-toxic could finally be realized in humans," Sillerud writes
in a research paper published last year in the Journal of Alzheimer's Disease.
The nanoparticles are digested within days of their injection. Sillerud adds
they are non-toxic because they are less concentrated than the amounts of
naturally occurring iron oxide in the brain.
Because SPIONS are coated with antibodies that specifically target the plaques
and tangles and inflammation, fewer are found in other organs of the research
mice, he says. He adds that before the nanoparticles are passed out of the body,
they are broken down. The nanoparticles have not appeared intact in feces or
A soon-to-be published paper in the same journal describes how those
nanoparticles imaged the reduction of the disease process after the mice were
fed resveratrol, a compound found in foods that inhibits inflammation, and a
similar synthetic compound, LD-55, named for its research creator Lorraine Deck.
The synthetic compound worked better than the natural one, he says.
He stresses that more research is required to support the work by duplicating
the results. A new round of research will test five more compounds developed
from starting points of known substances, such as one based on curcumin, the
active ingredient in curry that is thought to inhibit inflammation.
"People in India, where they eat lots of curry, don't have much Alzheimer's," he
says. "Many others have studied resveratrol and curcumin, but we have made
unique derivatives, which are the subject of UNM patents."
Neil Buckholtz, director of the Division of Neuroscience at the National
Institute on Aging, National Institutes of Health, says Sillerud's work is "very
interesting. But it's in the very early stages."
The ability to distinguish individual plaques, tangles and inflammation is
remarkable, he says, agreeing that imaging with MRI is more affordable than with
PET scans, which cost thousands of dollars each.
Recent funding increases at the NIA could allow funding of more research like
Sillerud's work and others, he says: "We got a significant allocation last week.
It's a good sign. Alzheimer's is a huge public health issue."
(c)2014 the Albuquerque Journal (Albuquerque, N.M.)
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