PRECLINICAL STAGES OF ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT MODELED WITH HESPEROS HUMAN-ON-A-CHIP® SYSTEM
-- Peer-reviewed publication in Alzheimer's & Dementia: Translational Research & Clinical Interventions validates potential of drug discovery platform and ability to study early stages of disease pathology --
ORLANDO, Fla. – May 28, 2020 – Hesperos Inc., pioneers of the Human-on-a-Chip® in vitro system, today announced a new peer-reviewed publication that describes how the company’s functional Human-on-a-Chip system can be used as a drug discovery platform to identify therapeutic interventions targeting the preclinical stages of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The manuscript, titled “A human induced pluripotent stem cell-derived cortical neuron human-on-a-chip system to study Aβ42 and tau-induced pathophysiological effects on long-term potentiation,” was published this week in Alzheimer's & Dementia: Translational Research & Clinical Interventions. The work was conducted in collaboration with the University of Central Florida and with David G. Morgan, Ph.D., Professor of Translational Neuroscience at Michigan State University, and expert in AD pathology.
To date, more than 100 potential therapeutics in development for AD have been abandoned or failed during clinical trials. These therapeutics relied on research conducted in preclinical animal studies, which often are unable to accurately capture the full spectrum of the human disease phenotype, including differences in drug metabolism and excretion between humans and animals. Therefore, there is a need for human models, especially those that accurately recapitulate the functional impairments during the preclinical phases of AD and MCI.
“Hesperos offers a breakthrough technology that provides a human cell-based assay based on cognitive function metrics to evaluate drugs designed to restore cognition at early stages of the Alzheimer’s continuum,” said Dr. Morgan. “This system can serve as a novel drug discovery platform to identify compounds that rescue or alleviate the initial neuronal deficits caused by Aβ1-42 and/or tau oligomers, which is a main focus of clinical trials.”
In 2018, Hesperos received a Phase I Small Business Innovation Research (SBIR) grant from the National Institute on Aging (NIA) division within the US National Institutes of Health (NIH) to help create a new multi-organ human-on-a-chip model for testing AD drugs. Research conducted under this grant included a study to assess therapeutic interventions based on functional changes in neurons, not neuronal death.
In the recent Alzheimer's & Dementia publication, Hesperos describes its in vitro human induced pluripotent stem cell (iPSC)-derived cortical neuron human-on-a-chip system for the evaluation of neuron morphology and function after exposure to toxic Aβ and tau oligomers as well as brain extracts from AD transgenic mouse models.
“Researchers are now focusing on biomarker development and therapeutic intervention before symptoms arise in AD and MCI,” said James Hickman, Ph.D., Chief Scientist at Hesperos and Professor at the University of Central Florida. “By studying functional disruption without extensive cell loss, we now have a screening methodology for drugs that could potentially evaluate therapeutic efficacy even before the neurodegeneration in MCI and AD occurs.”
The researchers found that compared to controls, treatment with toxic Aβ and tau oligomers or brain extracts on the iPSC cortical neurons significantly impaired information processing as demonstrated by reduction in high-frequency stimulation-induced long-term potentiation (LTP), a process that is thought to underlie memory formation and learning. Additionally, oligomer and brain extract exposure led to dysfunction in iPSC cortical neuron electrophysiological activity, including decreases in ion current and action potential firing.
While exposure to the toxic oligomers and brain extracts caused morphological defects in the iPSC cortical neurons, there was no significant loss in cell viability.
“Clinical success for AD therapies has been challenging since preclinical animal studies often do not translate to humans,” said Michael L. Shuler, Ph.D., Chief Executive Officer of Hesperos. “With our recent study, we are now one step closer in developing an AD multi-organ model to better evaluate drug metabolism in the liver, penetration through the blood-brain barrier and the effects on neuronal cells.”
About Alzheimer’s Disease / Preclinical Stage AD
AD is a progressive disease that is characterized by memory loss and deterioration of cognitive function. Preclinical AD is the first stage of the disease, and it begins long before any symptoms become apparent. It is thought that symptoms do not manifest until there is a significant death of neuronal cells, which is caused by the aggregation of toxic amyloid beta (Aβ) and tau oligomers, typically during the earliest stages of the disease. Unfortunately, treatment after the diagnosis of MCI may be too late to reverse or modify disease progression.
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About Hesperos Human-On-A-Chip®
Hesperos, Inc. is a leading provider of Human-on-a-Chip microfluidic systems to characterize an individual’s biology. 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 PKPD modeling of live physiological responses utilizing functional readouts from neurons, cardiac, muscle, barrier tissues and neuromuscular junctions as well as responses from liver, pancreas and barrier tissues. Created from human stem cells, the fully human systems are the first in vitro solutions to accurately predict in vivo functions without the use of animal models. More information is available at www.hesperosinc.com.
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