Innovative microfluidic device could transform drug testing for ALS
and other neurodegenerative diseases
ORLANDO, Fla.–(BUSINESS WIRE)– Hesperos, Inc. has increased its pioneering human-on-a-chip drug testing
capabilities by adding a new in vitro, human-human neuromuscular
model to its patented multi-organ microfluidic device systems. Abnormal
function of the neuromuscular junction is associated with
neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS)
and spinal muscular atrophy, and a human model will be critical in
developing and selecting effective drugs to treat these diseases.
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The breakthrough technology is described in a recent Biomaterials
paper by Hesperos CSO James Hickman from the Hybrid Systems Laboratory
at the University of Central Florida, “Stem
cell derived phenotypic human neuromuscular junction model for dose
response evaluation of therapeutics.” The technology is licensed to
Hesperos, and is currently available as a fee-for-service assay.
The BioMEMs construct is the first of its kind. Unlike other tests that
examine neuromuscular function in co-cultures or using biomarker
activity and protein analysis, Hickman’s model is a functioning platform
that recreates human neuronal connections to skeletal muscle. The
compartmentalized, serum-free microfluidic device is made with thin
silicone membrane with tiny tunnels. Nerve cells (motoneurons) and
skeletal muscle cells (myoblasts) cultivated from human stem cells are
plated on opposite sides of the membrane, creating a barrier that
provides electrical and chemical isolation.
Over the course of several days, the muscle cells fuse to form muscle
fibers (myotubes). The motoneurons project axons (long, slender
projections that conduct electrical impulses away from the nerve cell
body) through the microtunnels and form neuromuscular junctions with the
myotubes. These junctions serve as conduits for communication between
the two cell types, similar to what happens in the human body. The
result is mini muscles that can be contracted by motoneuron activation
or direct electrical stimulation.
Drugs can be applied to the model — in single doses or in several doses
over an extended period of time, mimicking real drug evaluation
conditions — to measure how the muscle system reacts. In the National
Institutes of Health funded study, Hickman describes dose response
curves his team generated for three drugs — curare toxin, alpha
bungarotoxin, and an approved drug, botulinum toxin (BOTOX®).
The results closely matched in vivo (live human) data at all four
stimulation frequencies tested, suggesting the model provides an
extremely accurate replica of live human systems, allowing rapid,
realistic, non-invasive drug testing — without the use of animals.
Hesperos has been recognized for its innovative alternatives to animal
testing, including the international 2015
Lush Prize for Science. Aside from the ethical considerations of
using live animal subjects to test drugs, animal testing is woefully
inaccurate. For every 50 drugs that are determined to be safe for
animals, only one proves safe in humans, and the FDA approval process
for drugs based on animal testing is a long one.
In contrast, the functional read-outs generated by Hickman’s model have
been closely correlating to what clinicians are observing in human
clinical trials. This could help inform the design of future clinical
trials, and accelerate drug development timelines.
“The model’s sensitivity in quantifying the degree of loss-of-function
caused by neuromuscular blocking agents with varying modes of action
provides a highly accurate and sensitive screening tool for new drugs,”
Hickman says. “It can also allow us to observe the behavior of
neuromuscular systems as a disease progresses, and inform treatment
decisions based on what patients are experiencing, as they experience
“Future iterations of this system with diseased motoneurons or muscle
could also be used to develop drugs to treat other neuromuscular
diseases,” adds Hesperos President and CEO Michael Shuler, founding
Chair for the Department of Biomedical Engineering at Cornell
University. “We’re excited to be able to add this capability to our
Hesperos, Inc, is a leader in efforts to characterize an individual’s
biology with human-on-a-chip microfluidic systems. Founders Michael L.
Shuler and James J. Hickman have been at the forefront of every major
scientific discovery in this realm, from individual organ-on-a-chip
constructs to fully functional, interconnected multi-organ systems. With
a mission to revolutionize toxicology testing as well as efficacy
evaluation for drug discovery, the company has created pumpless
platforms with serum-free cellular mediums that allow multi-organ system
communication and integrated computational modeling of live
physiological responses of functional neurons, cardiac, muscle, and
neuromuscular junctions as well as liver, pancreas and barrier tissues.
Created from human stem cells, the fully human systems are the first in
vitro solutions that accurately recreate in vivo functions
without the use of animal models, as featured
in Science. More information is available at http://www.hesperosinc.com
for Hesperos, Inc.
Michelle Linn, 774-696-3803
Source: Hesperos, Inc.