Neurotoxicity refers to adverse effects on the human brain or nervous system caused by chemical, physical or environmental factors. Researchers have long established links between neurotoxicity and exposure to some commonly used drugs and chemicals.
Symptoms of neurotoxicity are wide-ranging and dependent on the level of exposure to a given toxin. These symptoms can include (but are not limited to) headaches, fatigue, diminished cognitive function, imbalance and behavioral concerns including depression. Studies have also indicated that neurotoxicity contributes to more long-term, progressive neurological disorders including Alzheimer’s disease.
Current Challenges in Neurotoxicity Testing
The most effective solution to the issue of neurotoxicity is to conduct thorough pre-market testing of any new drugs or chemicals before they are cleared for public usage. However, current toxicity testing faces a number of challenges. For one, testing methods have grown organically over recent years, rather than as part of a more cohesive overall system. As a result, testing protocols and procedures are not necessarily consistent, and can be somewhat unwieldy with regard to time, expense and materials needed. In addition, the sheer number of drugs and chemicals that need to be tested in order to determine their potential for neurotoxicity creates a backlog that is difficult for scientists and researchers to manage (particularly since a high level of expertise is needed in order to successfully conduct these tests).
Scientists have also had to contend with a lack of specific biomarkers that more accurately and sensitively detect and predict relevant levels of neurotoxicity in a given chemical. Fluid-based biomarkers including plasma, serum, cerebral spinal fluid (CSF) and urine have shown great promise in this regard, as have advanced neuroimaging techniques, but more research is needed to assess their potential.
An Integrated, Proactive Response
Based in Washington, DC and in partnership with nearly 300 organizations throughout the world, the Health and Environmental Sciences Institute (HESI) is dedicated to improving safety and efficiency assessments in drug development and research. To that end, HESI has created the Translational Biomarkers of Neurotoxicity (NeuTox) Committee, with the goal of further researching and developing biomarkers of neurotoxicity. The committee is comprised of two working groups:
Translational Biomarkers of Neurotoxicity
This group is focused on identifying and evaluating non-invasive biomarkers for use in neurotoxicity testing. Non-invasive biomarkers are easier to sample and enable earlier detection of potential neurotoxicity in developmental drugs, further conserving costs and improving rates of clinical stage drug attrition. The fluid-based and neuroimaging biomarkers mentioned above form a key component of the team’s research.
Microelectrode Array Subteam
This subteam is studying the use of in vitro microelectrode array (MEA) technology as a means of examining seizure prediction. MEA is a comprehensive, non-invasive means of measuring electrical signals in cells. In this technique, a grid of electrodes is embedded in a well and active cells are placed on top of the grid; the electrodes then measure cell activity. MEA utilizes basic cell culture technology and is much less expensive and labor intensive than other methodologies such as a manual patch-clamp technique.
Expected Impacts
Through the research it is conducting, the NeuTox committee hopes to raise awareness of the need for more non-invasive biomarkers in neurotoxicity testing. This will, in turn, help streamline the clinical testing process and guide more informed and proactive decision making with regard to drug development.
Role of StemBioSys
StemBioSys aims to release their newest matrix product, NeuroMatrix, in December 2022. This astrocyte-derived ECM product recreates aspects of the neuronal niche with the intent of providing researchers with more biologically-relevant phenotypes of neurons in vitro. Using this technology, StemBioSys hopes to advance the work of the NeuTox committee by facilitating more predictive cell-based assays.