TY - JOUR
AU - Sandra H Blumenrath
AU - Bo Y Lee
AU - Lucie Low
AU - Ranjini Prithviraj
AU - Danilo Tagle
AB - Technological advances with organs-on-chips and induced pluripotent stem cells promise to overcome hurdles associated with developing medical products, especially for rare diseases. Organs-on-chips—bioengineered “microphysiological systems” that mimic human tissue and organ functionality—may overcome clinical trial challenges with real-world patients by offering ways to conduct “clinical trials-on-chips” (CToCs) to inform the design and implementation of rare disease clinical studies in ways not possible with other culture systems. If applied properly, CToCs can substantially impact clinical trial design with regard to anticipated key outcomes, assessment of clinical benefit and risk, safety and tolerability profiles, population stratification, value and efficiency, and scalability. To discuss how tissue chips are best used to move the development of rare disease therapies forward, a working group of experts from industry, academia, and FDA as well as patient representatives addressed questions related to disease setting, test agents for microphysiological systems, study design and feasibility, data collection and use, the benefits and risks associated with this approach, and how to engage stakeholders. While rare diseases with no current therapies were considered the ultimate target, participants cautioned against stepping onto too many unknown territories when using rare disease as initial test beds. Among the disease categories considered ideal for initial CToC tests were well-defined diseases with known clinical outcomes; diseases where tissues on chips can serve as an alternative to risky first-in-human studies, such as in pediatric oncology; and diseases that lend itself to immuno-engineering or genome editing. Participants also considered important challenges, such as hosting the chip technology in-house, the high variability of cell batches and the resulting regulatory concerns, as well as the financial risk associated with the new technology. To make progress in this area and increase confidence with the use of tissue chips, the re-purposing of approved drugs ought to be the very first step.
BT - Experimental Biology and Medicine
DA - 2020-7
DO - 10.1177/1535370220924743
IS - 13
N2 - Technological advances with organs-on-chips and induced pluripotent stem cells promise to overcome hurdles associated with developing medical products, especially for rare diseases. Organs-on-chips—bioengineered “microphysiological systems” that mimic human tissue and organ functionality—may overcome clinical trial challenges with real-world patients by offering ways to conduct “clinical trials-on-chips” (CToCs) to inform the design and implementation of rare disease clinical studies in ways not possible with other culture systems. If applied properly, CToCs can substantially impact clinical trial design with regard to anticipated key outcomes, assessment of clinical benefit and risk, safety and tolerability profiles, population stratification, value and efficiency, and scalability. To discuss how tissue chips are best used to move the development of rare disease therapies forward, a working group of experts from industry, academia, and FDA as well as patient representatives addressed questions related to disease setting, test agents for microphysiological systems, study design and feasibility, data collection and use, the benefits and risks associated with this approach, and how to engage stakeholders. While rare diseases with no current therapies were considered the ultimate target, participants cautioned against stepping onto too many unknown territories when using rare disease as initial test beds. Among the disease categories considered ideal for initial CToC tests were well-defined diseases with known clinical outcomes; diseases where tissues on chips can serve as an alternative to risky first-in-human studies, such as in pediatric oncology; and diseases that lend itself to immuno-engineering or genome editing. Participants also considered important challenges, such as hosting the chip technology in-house, the high variability of cell batches and the resulting regulatory concerns, as well as the financial risk associated with the new technology. To make progress in this area and increase confidence with the use of tissue chips, the re-purposing of approved drugs ought to be the very first step.
PY - 2020
SP - 1155
EP - 1162
ST - Tackling rare diseases
T2 - Experimental Biology and Medicine
TI - Tackling rare diseases: Clinical trials on chips
UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400726/
VL - 245
Y2 - 2023-08-29
SN - 1535-3702
ER -