In a recent interview, Emily Richardson, Lead Scientist at CN Bio, delved into the intricacies of drug development and the pivotal role of microphysiological systems (MPS) in bridging the gap between in vitro models and human responses. The discussion highlighted the challenges faced during drug development, particularly in translating preclinical data to clinical outcomes. Traditional methods often fall short due to physiological differences between animal models and humans. MPS, also known as Organ-on-a-chip (OOC), offers a promising solution by providing more accurate and translatable data, thereby enhancing safety and efficacy assessments.
The journey of drug development is fraught with complexities. Ensuring that a therapeutic compound is both effective and safe requires rigorous testing across various models. Preclinical studies aim to predict how a drug will behave in humans, but discrepancies arise because in vitro models are typically limited to specific cell types, while in vivo models, despite representing whole systems, do not fully replicate human physiology. This limitation becomes especially critical in safety and toxicology evaluations, where even minor inaccuracies can lead to significant failures in clinical trials.
New methodologies, such as microphysiological systems, offer a bridge between these two approaches. These systems incorporate human cells and mimic the complex interactions within organs, providing higher translatability and physiological relevance. For instance, CN Bio's PhysioMimix OOC platform allows for the recreation of liver tissue, complete with fluidic flow and biomechanical stimuli, which closely resemble natural conditions. This setup enables researchers to gain deeper insights into drug metabolism, toxicity, and pharmacodynamics, ultimately leading to better predictions of clinical outcomes.
One of the key applications of MPS technology is in assessing drug-induced liver injury (DILI). Liver toxicity remains a major cause of drug failures, accounting for nearly 30% of cases. MPS platforms, equipped with human hepatocytes and immune system components, can detect both intrinsic and idiosyncratic DILI events. Intrinsic DILI, characterized by dose-dependent and predictable reactions, can be identified using standard assays. However, idiosyncratic DILI, which exhibits latent onset and is influenced by genetic and environmental factors, requires more sophisticated models like those provided by MPS. These models can sustain functional hepatocytes for extended periods, allowing for the study of chronic toxicity and providing valuable mechanistic insights.
MPS technology not only enhances preclinical safety testing but also contributes to the three R’s—replacement, reduction, and refinement—of animal testing. By offering human-relevant outcomes, MPS reduces the reliance on animal models, thereby minimizing costs, time, and ethical concerns. CN Bio has made significant strides in qualifying its liver MPS models, collaborating with regulatory bodies like the FDA to ensure their reliability. The company's ongoing efforts to develop multi-organ and interspecies MPS models further underscore the potential of this technology in improving drug development processes.
In conclusion, the integration of microphysiological systems into drug development workflows promises to revolutionize the field. By providing more accurate and translatable data, MPS can help identify safer and more effective therapeutics, ultimately benefiting patients and reducing the risks associated with clinical trials. As research continues to advance, the potential of MPS to transform preclinical testing and improve patient outcomes becomes increasingly evident.