Horizon eBook - 6

Innovations in Cell-Based Screening * Phenotypic Screens Rise in Popularity

Researchers at Columbia University Medical
Center are using phenotypic, high-throughput
screening platforms targeting cellular pathways
to Alzheimer's, including beta secretase (BACE
1) inhibitors, Tau protein modulators, and
apolipoprotein E (ApoE) enhancers in primary
and stem cell-derived neurons and glial cells.
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surrogate cell studies, robust cell-line development,
imaging and analytics technology, and high-throughput target prioritization.
"The idea is to adjust the discovery paradigm,"
continues Dr. Vogt. "Combine the benefits of
high-throughput approaches with those of more
relevant biological approaches."
Imaging and analytics figure prominently in some
new tools for carrying out phenotypic screening.
Animated Dynamics (Anidyn), for example, has
developed a biodynamic imaging platform that uses
holography and laser radar to measure changes in
human tissue in real time. The technology, which
offers a clear view of how tumor and other cells
respond to different drugs and drug dosages, has
undergone preclinical testing and will soon be tested
in human clinical trials. The company, which licenses
the technology from Purdue, expects to receive
regulatory approval and to launch commercial
sales by 2017.
David Nolte, Ph.D., physics professor at Purdue
and president of Anidyn, says the platform will provide a biologically relevant context to lead selection.

"The biology happening in petri dishes during lead
testing is not the biology that goes on within tissue,
notes Dr. Nolte. "There are differences in how cells
respond to drugs in a three-dimensional environment, which means the results that occur in Petri
dishes may not be the same as the results that
occur in the body."
"We use spectroscopy to measure the timedependent changes in the hologram," adds John
Turek, the company's executive vice president and
CFO. "It breaks down the changes into different
frequencies, and we can tell how a cell's membranes,
mitochondria, nucleus, and even cell division respond
to drugs. We measure the frequency of the light fluctuations as a function of time after a drug is applied."
The platform makes digital holograms of
tissues, allowing for visualization, not just at the
surface, but throughout the tissue. The technology
can also visualize the effects of drugs over time.
It will be marketed for use in personalized cancer
treatment to help physicians develop the most
effective treatments and as a companion diagnostic
to optimize patient selection for clinical trials.



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Horizon eBook

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