NIH Awards $35.5 Million to Use Tiny, Bioengineered Organ Models to Improve Clinical Trials’ Development and Design

September 29, 2020 

Clinical Trials on a Chip researchers plan to build and test common and rare disease models to help improve the clinical trial process.

A tissue model of catecholaminergic polymorphic ventricular tachycardia (CPVT), a leading cause of sudden death from cardiac arrest in children and young adults, on a tissue chip. Scientists from Boston Children’s Hospital and Harvard University reprogrammed blood cells from a patient with a gene mutation linked to most cases of CPVT and prompted these cells to become stem cells. These in turn were made into cardiomyocytes (heart muscle cells) carrying CPVT mutations, which were seeded onto an engineered surface. The cells, shown in purple, lined up in a direction similar to how heart muscle is organized and beat together. (Sung Jin Park/Boston Children’s Hospital and Donghui Zhang/Harvard SEAS)

Approximately 85% of late-stage clinical trials of candidate drugs fail because of drug safety problems or ineffectiveness, despite promising preclinical test results. To help improve the design and implementation of clinical trials, the National Institutes of Health has awarded 10 grants to support researchers’ efforts in using tiny, bioengineered models of human tissues and organ systems to study diseases and test drugs. One major goal of the funded projects is to develop ways to better predict which patients are most likely to benefit from an investigational therapy prior to initiating clinical trials.  

The awards total more than $6.9 million in the first year, and approximately $35.5 million over five years, pending available funds. They are administered through a new program, Clinical Trials on a Chip, which is led by NIH’s National Center for Advancing Translational Sciences (NCATS) in conjunction with several other NIH Institutes and Centers, including the National Cancer Institute, the National Institute of Child Health and Human Development, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Tissue chips, or organs-on-chips, are 3-D platforms engineered to support living human tissues and cells and mimic complex biological functions of organs and systems. Tissue chips are currently being developed for drug safety and toxicity testing and disease modeling research, including on the International Space Station. Clinical Trials on a Chip is one of several initiatives that are a part of the NCATS-led Tissue Chip for Drug Screening program, which was started in 2012 to address the major gaps in the drug development process.

The projects are organized into two phases. In the first phase, the grantees will develop tissue chip models of disease. They also will develop biological indicators from the chips that correlate with clinical condition and enable scientists to determine the progression of a disease and effectiveness of a therapy. In the second phase, the researchers will evaluate the usefulness of the disease models by testing candidate therapies and, in some cases, collaborating with pharmaceutical and biotech companies to compare patient results with that of the corresponding patient chips.

Many of these therapies will be tested in tissue chips in parallel to patients in clinical trials. In one project, for example, scientists plan to develop a tissue chip model of two types of muscular dystrophy, a muscle-wasting disease, to study the effects of a promising drug candidate already being tested in patients. Another team of researchers plans to develop a bone marrow model to determine which patients with treatment-resistant prostate cancer that has spread to the bone might benefit from a new therapy that also is being tested in patients.

The new grantees bring expertise in clinical trial design, disease biology, engineering, pharmacology, computational biology and more. They will study a range of common and rare diseases, such as prostate cancer, pediatric disorders, kidney disease, heart disease, fatty liver disease and a disease that causes premature aging as well as premature birth.

“Our hope is to eventually impact the fundamental way we do clinical trials,” said Danilo Tagle, Ph.D., NCATS associate director for special initiatives, who oversees the program, along with scientific program manager Passley Hargrove-Grimes, Ph.D. “We want to see if tissue chips can be a useful platform in which to help researchers preempt some potential challenges with trials. The teams have to make sure the models are valid and show that data from tissue chips accurately reflect results in people. If tissue chip data can predict which patient populations might benefit the most from investigational drugs, this information could potentially improve clinical trial success rates.”

From NIH: National Center for Advancing Translational Sciences,