In the realm of drug development, animals like rodents and non-human primates have proven instrumental in assessing the safety and efficacy of many potential treatments. However, the increasing availability of innovative technologies—such as organ-on-a-chip, fat-on-a-chip, nerve-on-a-chip, and organoid models—is heralding a shift towards new alternative methods (NAMs) of drug testing. Today’s Tulane Digest delves into the exciting advancements in the field as a whole and highlights some of the transformative contributions by academia and start-ups that are propelling us toward a more efficient future for preclinical drug testing.
The Need for Change and the FDA Modernization Act
The utilization of animals in drug development has historically been driven by a lack of viable alternatives. With the passage of the FDA Modernization Act in December 2022, a paradigm shift has been initiated. As part of the new drug application process, pharmaceutical companies are now required to submit preclinical data on their compounds before proceeding to human clinical trials. Even with the use of extensive animal studies in drug development, translation gaps leading to high attrition rates, toxicological concerns, inconsistent replication of results in humans, and suboptimal efficacy profiles have persisted. This has intensified calls for reform and accelerated the exploration of NAMs for drug testing.
Introducing New Alternative Methods
NAMs encompass a wide range of innovative approaches, including cell-based assays, organ-on-a-chip technologies, computer modeling (including some applications of ), and micro-physiological systems. These cutting-edge methodologies enable researchers to study the impact of compounds or environmental factors on human biological systems, bridging the gap between animal models and the human body. By utilizing NAMs, the understanding of how active ingredients function in a human model is greatly enhanced before progressing to human testing.
Promising Breakthroughs
Organ-on-a-chip and organoid research have made incredible breakthroughs in recent years and can be found in research institutions and start-up companies alike. The India Institute of Science has done prolific work on a heart-on-a-chip model to study cardiovascular diseases. Seoul National University has done extensive work in the realm of kidney-on-a-chip models, highlighting that microfluidic chips can very closely resemble in vivo modeling. Tulane University’s Dr. Ryosuke Sato also focuses on kidney alternatives in the form of kidney organoids. Dr. Sato’s in vitro kidney organoids are cultured and created from stem cells to form a system that mimics the function of human kidneys. Once formed, these kidney organoids can be challenged in drug toxicity experiments to screen for compounds that have the highest chances of safety.
Startups with promising alternative drug testing technologies include Obatala Sciences, Emulate Bio, and AxoSim. Obatala Sciences is led by CEO Trivia Frasier, PhD, MBA, and they have created a breakthrough technology that has immense applications in various organ-on-a-chip models, providing an accurate representation of human organ environments. Obatala Sciences develops and commercializes many organ-on-a-chip models that researchers use for drug testing and therapeutic discovery, such as ObaGel®, the first commercially available human-derived hydrogel. Further, research from Harvard’s Wyss Institute led to the creation of Emulate Bio, a start-up with products that include kidney-chip, lung-chip, and liver-chip technologies among others. Finally, AxoSim—which was founded by Michael Moore, PhD, and Lowry Curly, PhD, of Tulane University—specializes in nerve-on-a-chip technologies that enable the identification of superior drug candidates earlier, with heightened accuracy and efficiency. AxoSim has several state-of-the-art biomimetic platforms, including 3D human-relevant myelination platforms that are used for neuro-pharmaceutical testing. Each of these commercial technologies provides a unique opportunity to evaluate the potentially toxic effects of drug compounds quickly and accurately without the use of animal sacrifice.
Embracing an Efficient Future
By advocating for the use of alternative methods for drug screening and testing, we take a significant stride towards a world that is more efficient in bringing therapeutics to market. These innovative approaches are often not only more cost-effective than animal testing but also expedite the drug development process. The integration of alternative methods in preclinical drug testing signifies remarkable progress, and as research continues in this area, there is hope that the drug development process can move forward with fewer animal sacrifices and more robust data packages.
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The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2023 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.
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Curated Research and Research-Related News Summaries, Analyses, and Syntheses. Published on behalf of The Tulane University School of Medicine. Content is generated by reviewing scientific papers and preprints, reputable media articles, and scientific news outlets. We aim to communicate the most current and relevant scientific, clinical, and public health information to the Tulane community – which, in keeping with Tulane’s motto, “Not for Oneself but for One’s Own”, is shared with the entire world.
Kaylynn J. Genemaras, PhD: Editor-in-Chief
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Special thanks to James Zanewicz, JD, LLM, RTTP, and Elaine Hamm, PhD, for copyediting assistance