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New Dye that Binds to Alzheimer's Plaques Could
Offer Early Diagnosis
NIAD-4 dye could be ready for clinical trials in near
future
Aug. 25, 2005 – MIT scientists have developed a new
dye, called NIAD-4, that can bind to the protein deposits, or plaques,
in the brain that cause Alzheimer's, and then show fluorescence when
exposed to radiation. The potential is that this discovery can lead to
noninvasive early diagnosis, help in monitoring the progress and the
study of new treatments of Alzheimer’s disease.
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Today, doctors can only make a definitive diagnosis
of Alzheimer's -currently the fourth-leading cause of death in the
United States - through a postmortem autopsy of the brain.
This test involved mice, but Timothy Swager, leader
of the work and a professor in MIT's Department of Chemistry says
fluorescing dyes like NIAD-4 could be ready for clinical trials in the
near future.
"Before you can cure Alzheimer's, you have to be
able to diagnose it and monitor its progress very precisely," said
Swager. "Otherwise it's hard to know whether a new treatment is working
or not."
To that end, Swager and postdoctoral associate
Evgueni Nesterov, also from the MIT Department of Chemistry, worked with
researchers at Massachusetts General Hospital and the University of
Pittsburgh to develop the new dye, which could allow direct imaging of
Alzheimer's plaques through a patient's skull.
Some of the first noninvasive techniques for
diagnosing Alzheimer's involved agents labeled with radioactive elements
that could enter the brain and target disease plaque for imaging with
positron emission tomography (PET). These methods, however, are
expensive and limited by the short working lifetime of the labeled
agents.
Swager and colleagues developed the new dye -
NIAD-4 - through a targeted design process based on a set of specific
requirements, including the ability to enter the brain rapidly upon
injection, bind to amyloid plaques, absorb and fluoresce radiation in
the right spectral range, and provide sharp contrast between the plaques
and the surrounding tissue. The compound provided clear visual images of
amyloid brain plaques in living mice with specially prepared cranial
windows.
To make the technique truly noninvasive, scientists
must further refine the dye so it fluoresces at a slightly longer
wavelength, closer to the infrared region. Light in the near-IR range
can penetrate living tissue well enough to make brain structures
visible. Swager likens the effect to the translucence produced when one
holds a red laser pointer against the side of a finger.
"This procedure could be done in a chamber with a
photodetector and a bunch of lasers, and it would be painless," he said,
adding that infrared fluorescence and other optical techniques will lead
to a whole new class of noninvasive medical diagnostics.
"What we have is a dye that lights up when it binds
to amyloids that form in the brains of people with Alzheimer's. It's a
completely new transduction scheme-a way of translating a physical or
chemical event that's invisible to the naked eye, into a recognizable
signal. Further wavelength adjustments in these dyes will allow us to
perform in vivo analysis through human tissue."
The new dye was developed as part of a broader
effort in sensing technology at MIT's Institute for Soldier
Nanotechnologies. In addition to its applications as a medical
diagnostic, Swager says fluorescing dyes like NIAD-4 could work as
signals in a wide variety of sensing schemes.
The work will be published in the Aug. 26 issue of
Angewandte Chemie.
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