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Small Business Grant Funds Blood-Brain Barrier Model

ParVivo chip

ParVivo chip platform (Nortis Inc.)

18 August 2017. A spin-off company from University of Washington is developing a chip device emulating the blood-brain barrier that prevents many drugs from treating neurological disorders. The device is a creation of Nortis Inc. in Seattle, the recipient of a $688,000 Small Business Innovation Research grant from National Institute of Neurological Disorders and Stroke,or NINDS, part of National Institutes of Health, extending the project into a third year.

Blood vessels in the brain form a support network for brain functions, with tightly-packed cells lining blood vessels that allow nutrients to pass through, but keeping out foreign substances. This barrier also keeps out drugs to treat neurological conditions, such as Parkinson’s or Alzheimer’s disease, and its impaired functioning is also implicated in these disorders. So far, no efficient method is available to penetrate this barrier that prevents some 98 percent of current drugs from reaching the brain or central nervous system.

Because the blood-brain barrier represents a special challenge to developing treatments for neurological diseases, drug makers need better tools for addressing this problem. Nortis proposed to NINDS creating a model of the blood-brain barrier that provides drug makers with a means of reliably testing potential neurological treatments, before human clinical trials or even preclinical animal tests.

“Understanding how drugs are transported across the blood-brain barrier and interact with the brain presents a significant scientific challenge,” says Thomas Neumann, Nortis’s CEO in a company statement. “More predictive preclinical models based on human tissue are urgently needed to reduce costs and minimize clinical trial failures.”

The model, based on the company’s ParVivo platform, is a microfluidics or lab-on-a-chip plastic device made with fine channels and tissue cells representing blood vessels arrayed in an architecture like that in the brain. The channels have endothelial cells lining blood vessels supported by pericyte cells that control the flow of blood through the vessels. In addition, astrocytes that form the glial support network in the brain are part of the model. The company says the endothelial cells, pericytes, and astrocytes can self-assemble in the model.

Nortis is first developing a version of the model for a mouse blood-brain barrier that the company will use to test basic blood-brain functions, including transfer of proteins. A second stage, still with a mouse model, will test for more complex functions, such as the transfer of lipopolysaccharides, large molecules found on the membranes of Gram-negative bacteria, causing serious infections. The project’s third stage, a human blood-brain model, will be based on the lessons derived from the first two stages, and optimized for relevance to clinical outcomes.

Nortis was founded in 2012 by faculty at University of Washington to develop lab-on-chip devices representing tissues and organs to advance preclinical research on treatments for disease, and limit the use of animal testing.

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