Preclinical trials and studies of all kinds involve a number of different types of testing, including in vivo, in situ, in silico, and in vitro testing.
Briefly, in vivo testing is performed in or on a whole living organism (usually an animal), in situ testing occurs where the organism is found in nature, while in silico testing describes computer models designed to map or replicate biological functions. In vitro testing is performed outside of the whole living organism as part of proof of concept (POC). Utilizing tissue samples, isolated organs and cell cultures, explants, cell lines, and even subcellular fractions, in vitro testing allows for fast, repeatable, controllable tests. These cells or tissues are grown in a lab environment and used to study effects without the need of living subjects.
Neuropharmacology is investing more in in vitro testing. However, the rise of in vitro testing in neuropharmacology is a relatively recent development.
There are no shortcuts in neuropharmacology, and recent investments in in vitro experimental models have allowed neuropharmacologists to better understand their compounds during the POC phase.
In vitro tests are inexpensive and relatively easy to set up, and they are also highly repeatable and controllable, compared even to animal studies. Using everything from very specific cells to brain slices showing whole brain architecture, in vitro tests are able to prove mechanism of action (MoA) or discover neurotoxic effects early in the process before in vivo testing is performed.
Recent developments such as human iPSC derived neurons and microelectrode arrays (MEA) have enabled scientists to explore in vitro studies that would have been impossible just a few years ago.
In vitro testing in neuropharmacology still does not always map perfectly to a human brain.
Unfortunately, the single biggest drawback of animal studies for neuropharmacology is one that in vitro studies often share. The extreme complexity of the human brain makes mapping results from animal studies onto real-world effects nearly impossible, and the same is true of in vitro studies. Potency, efficacy, drug-drug interactions, and even the behavior of the drug itself may prove very different in an animal brain or an in vitro model than in an actual end user.
While in vitro testing uses materials derived from actual human or animal tissues to more closely model neuronal activity, and may therefore provide a closer match to the functioning human brain than an animal model, the responses observed in vitro may be very different when the same intervention is applied to an integrated system. Furthermore, even our most advanced models are inadequate for assessing the totality of the brain’s complex neuronal action.
In spite of the drawbacks that still exist, in vitro testing for neuropharmacology offers many benefits.
Compared to in vivo testing, the experimental setup of in vitro neuropharmacology is relatively simple and more reproducible than some animal studies. While in vitro studies lack the animal welfare and social concerns that come with in vivo testing, they bring their own concerns about ethics and standards, which is why guidelines and regulations are vitally important, as is working with an accredited organization like QPS. These guidelines and standards help keep all preclinical testing safe, ethical, and humane.
Compared to in vivo testing, in vitro studies are quick and easy to set up, inexpensive, and require a comparatively small amount of test material. Perhaps more importantly, in vitro testing makes it easier to implement experimental controls, and tests are more repeatable with high quality control and a vast range of possible applications.
Ultimately, in vitro testing should be the first step in a robust neuropharmacology testing process, which also includes in silico, in vivo, and clinical trials in human subjects, as appropriate. Used correctly, in vitro studies can help neuroscientists obtain valuable data and speed up the development of needed drugs and interventions.
Since 1995, QPS has provided discovery, preclinical, and clinical drug development services. An award-winning leader focused on bioanalytics and clinical trials, QPS is known for proven quality standards, technical expertise, a flexible approach to research, client satisfaction, and turnkey laboratories and facilities. For more information, please email [email protected] or visit www.qpsneuro.com. You can also learn more about QPS Austria’s CAA research in our June 2019 newsletter, which you can find at https://qpsneuro.com/newsletter.