Attacking Alzheimer’s: Human-on-a-chip model could lead to better treatments

Alzheimer’s is a “devastating memory-wasting disease that has continually seen failure after failure in the clinic,” according to an article by Ben Adams in Fierce Biotech. With no cure yet in sight, a medical technology company in Florida has taken a new approach to simulating a human with the condition.

Hesperos, an Orlando-based company that to characterize an individual’s biology with human-on-a-chip microfluidic systems, has garnered National Institutes of Health (NIH) funding for Alzheimer’s “human-on-a-chip” trials. The company received a phase 1 grant from the National Institute on Aging in order to “realistically mimic the biology of Alzheimer’s disease (AD), and the effects of potential new therapies under realistic human physiological conditions,” NIH said.

Company researchers are going to create multi-organ models that use both healthy brain cells developed from pluripotent stem cells, and cells with different mutations that are consistent with Alzheimer’s.

Typically, such chips are ”lined with human cells and are designed to mimic the chemical and mechanical characteristics of their target tissue,” the article related. These devices have been developed because of the availability of microchip fabrication processes that can create tiny channels that, in the example of the lung-on-a-chip, accommodate the artificial lung and also simulate inhaling and exhaling. For this project, Hesperos is seeking to assemble a deeper model, including more organs to gain a better understanding of the ways in which therapeutic attempts are working. For that reason, the device is labeled a human-on-a-chip moniker, rather than just being a simulation of an organ.

Hesperos is creating a three-organ system that incorporates brain cells (cortical neurons) and functioning liver and blood-brain-barrier assemblies, in addition to recirculating blood and cerebral spinal fluid surrogates. The researchers hope that by mimicking key parts of the human body, they can determine the body’s reaction to new drugs being routed through it, including the method in which it acts on the liver (to determine toxicity) and the way in which it passes the blood-brain barrier. The researchers will create models using both healthy brain cells assembled from pluripotent stem cells, and cells with various mutations linked with the disease.

In the future, Hesperos is planning to determine long-term effects in its models, as well as real patient samples, to test its “viability as a tool to inform real-time, personalized treatment decisions as part of precision medicine.” Hesperos founders Michael Shuler, Ph.D., and James Hickman, Ph.D., are pioneers in organ-on-a-chip technology. Hesperos said it is the first company to develop pumpless microfluidic multi-organ systems with completely integrated physiological functions, including blood circulation and nerve connections.

Hickman, Hesperos’s chief scientist and a professor at the University of Central Florida’s Hybrid Systems Laboratory, explained, “There are estimated to be 50 million people in the world with dementia—that’s more than the population of Spain, and it is projected to nearly triple by 2050. Many of the people with dementia have AD, resulting in an urgent need for new, effective treatment options for the disease. Development of a low-cost, easy-to-use system to assess drugs for AD would improve efficacy and toxicological evaluations for patient specific treatments, providing a significant benefit to the drug development community and patients.”