Filipino savant crafts hi-tech Organs-on-Chips vs diseases

Human organs on a stick.

That is how Dr. Danilo A. Tagle, a Filipino-American scientist, describes “bioengineered Organs-on-Chips” whose development he is steering at the U.S. National Institutes of Health (NIH), one of the world's leading health research institutions.

Dr. Tagle, Associate Director for Special Initiatives at the NIH National Center for Advancing Translational Sciences, left the Philippines at the age of 18. This summer, he was back for a visit as Chair of the Scientific Advisory Committee on Health at the Philippine Genome Center (PGC).

The bioengineered organs are placed in a device “similar in size to a USB memory stick,” he told a scientific symposium on genomics at the PGC, the country's most advanced gene-related research complex located at the University of the Philippines Diliman.

The PGC leads local genomics research, a discipline in genetics studies that sequences, assembles and analyzes the function and structure of genomes or the complete set of DNA within a single cell of an organism.

Genomics research can lead to the development of new drugs, new diagnostic tools, new insights into the molecular mechanisms of diseases and tailor pharmaceuticals to individual needs.

Dr. Tagle leads and manages the NIH Microphysiological Systems and the Extracellular RNA Communication programs. Before joining the NIH, he was a Program Director for Neurogenetics at the U.S. National Institute of Neurological Disorders and Stroke where he was involved in developing programs in genomics-based approaches for basic and translational research in inherited brain disorders.

Since 1993, he was an Investigator and Section Head of Molecular Neurogenetics at the U.S. National Human Genome Research Institute where he was involved in the positional cloning of genes for Huntington's disease, ataxia-telangiectasia and Niemann-Pick type C disease.

(Huntington's is an inherited disease that causes the progressive degeneration of nerve cells in the brain; Ataxia-telangiectasia is a rare and inherited childhood disorder that affects the nervous, immune and other body systems; Niemann-Pick type C is an inherited disease that causes progressive deterioration of the nervous system.)

“Advances in basic and preclinical science continues to fuel the drug discovery pipeline,” Dr. Tagle said. “However, only a small fraction of compounds meet the criteria for approval by the U.S. Food and Drug Administration (U.S. FDA).”

He said more than 30 percent of promising medications have failed in human clinical trials because they are found to be toxic; this, despite promising pre-clinical studies in animals. Another 60 percent fail because they are not effective, he said.

“The challenge of accurately predicting drug toxicities and efficacies is in part due to inherent species differences in drug metabolizing enzyme activities and cell-type specific sensitivities to toxicants,” Dr. Tagle said.

To address this challenge in drug development and regulatory science, the U.S. NIH invested $70 million on the five-year Microphysiological Systems that Tagle heads. The so-called Organs-on-Chips Program aims to develop alternative approaches that would enable early indications and potentially more reliable readouts of toxicity and efficacy.

The Organ-on-Chips Program is a partnership between the NIH, the U.S. FDA and the Defense Advanced Research Projects Agency, a U.S. military think-tank that was instrumental in the early development of the Internet.

The program hopes to develop bio-engineered microdevices that represent functional units of the 10 major human organs: circulatory, respiratory, integumentary, reproductive, endocrine, gastrointestinal, nervous, urinary, musculoskeletal and immune systems.

“The opportunities for significant advancements in the prediction of human drug toxicities requires a multi-disciplinary approach that relies on an understanding of human physiology, stem cell biology, material sciences and bioengineering,” Tagle said.

The Organ-on-Chips Program, he said, is a unique and new platform which “could help ensure that safe and effective therapeutics are identified sooner and ineffective or toxic ones are rejected early in the drug development process.”

The microfabricated devices are useful for modeling human diseases and may prove to be sufficient alternatives to the use of animal models, Tagle said. (SciencePhilippines)