First Functional Stem-Cell Derived Neuromuscular Junction Model Licensed

ORLANDO, FLA – April 25, 2018 -- 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.


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 it.”

“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 human-on-a-chip toolkit.”

Overcoming a Big Barrier: Hesperos CEO awarded for Blood-Brain Barrier Innovation

Getting drugs past the neuroprotective blood-brain barrier (BBB) has been a perplexing problem and formidable challenge for researchers and pharmaceutical companies alike.


Hesperos’s creation of a microfluidic model capable of mimicking in vivo characteristics of the blood-brain barrier for prolonged periods was therefore widely welcomed, and recently earned CEO Michael L. Shuler recognition from the American Chemical Society.


At ACS’s Annual Meeting in New Orleans, Shuler was announced as the recipient of the Biotechnology & Bioengineering Gaden Award, named after Biotechnology & Bioengineering founding editor Elmer Gaden, Jr., in recognition of a high-impact paper reflecting exceptional innovation, creativity and originality.


Shuler, who is also the Samuel B. Eckert Professor of Engineering in the Meing School of Biomedical Engineering and in the Smith School of Chemical and Biomolecular Engineering at Cornell University,

was awarded for his paper “Microfluidic Blood-Brain Barrier Model Provides In Vivo-Like Barrier Properties for Drug Permeability Screening.”

As described in the paper, Shuler’s lab derived brain microvascular endothelial cells from human induced pluripotent stem cells and co-cultured them with rat glial cells on two sides of a porous membrane on a pumpless microfluidic platform for up to 10 days. The “BBB-on-a-chip” was engineered with wall shear stress and trans-endothelial electrical resistance in mind, and was tested for drug permeability using several large molecules and model drugs, including caffeine, cimetidine, and doxorubicin.


“Our BBB-on-a-chip model closely mimics physiological BBB barrier functions and will be a valuable tool for screening of drug candidates,” Shuler wrote.


The technology can now being incorporated into Hesperos’s multi-organ-on-a-chip systems. Visit here to learn more.

Hesperos Multi-Organ System Featured in Science

The challenge: Build microfluidic devices that can keep cells alive in a setting that mimics specific organs or tissues, and incorporate biosensors to measure the cells’ physiology. The goal: Mimic diseases and test drug responses that traditional 2D culture systems and animal models have been unable to predict, filling a critical gap in drug development and potentially lowering the cost of drug development, with increased speed and accuracy.


Several labs have risen to the challenge, creating a variety of organ-on-a-chip systems. Hesperos is pioneering the fully functional multi-organ system, and CEO Mike Shuler was featured recently in Science discussing some of the challenges the company has faced making the revolutionary technology a reality.


“There’s just a lot of things that can go wrong when somebody tries to do this,” admits Shuler, Samuel B. Eckert Professor of Engineering in the Meing School of Biomedical Engineering and in the Smith School of Chemical and Biomolecular Engineering at Cornell University.


For instance, the difference in solubility between oxygen and carbon dioxide in the cells’ medium can cause gas bubbles to accumulate over time, disrupting the system’s tightly controlled fluid flows and causing a problem during extended metabolic testing. Hesperos’s solution? Eliminating the pumps normally used to control microfluidic devices, and using a carefully designed gravity flow system instead.


Shuler also discusses the company’s business model, which involves offering multiorgan models as a service, rather than trying to sell and support them as stand-alone products. Clients so far include several pharmaceutical companies who have tested drugs on systems with four or five interconnected organs, including the liver, the heart, and neuromuscular junctions, as well as artificial skin, gastrointestinal tracts, and models of the blood–brain barrier.


Read the full story here.

Hesperos President Wins 2018 B&B Gaden Award

Hesperos President Dr. Mike Shuler has won the 2018 Biotechnology and Bioengineering Gaden Award! The Gaden Award is named in honor of Elmer L. Gaden, Jr., the founding editor of Biotechnology & Bioengineering, and is given in recognition of a truly outstanding paper published in the journal during the last year.

The paper selected for recognition this year was Microfluidic Blood-Brain Barrier Model Provides In Vivo-Like Barrier Properties for Drug Permeability Screening, found in Volume 114, Issue 1, January 2017.

Shuler Highlighted by CNBC as Founder of Organ-on-a-Chip Industry

Hesperos president Michael Shuler first coined the term "animal-on-a-chip" (and now "human-on-a-chip") back in 1990.  Starting as part of his research to define the multidisciplinary field, human-on-a-chip systems are quickly becoming an industry destined drastically reduce pharmaceutical development costs.  

Click here to learn more about the industry and Dr. Shuler's contribution in the article published by CNBC.

Awards Granted for Innovation by SLAS Technology

Congratulations to Dr. James J. Hickman and Dr. Michael L. Shuler on being recognized for their publication in the JALA paper entitled “TEER Measurement Techniques for In Vitro Barrier Model Systems”.

They are to be honored with the 2017 SLAS Technology Readers Choice Award (reflecting popularity among readers throughout 2016) AND the 2017 SLAS Technology Authors Choice Award (reflecting popularity among authors – citations – throughout 2016).

The reception will be held on Feb. 6th, 2017 at the Washington, DC Convention Center.