ToxChats©

In this podcast, Dr. Tetyana Cheairs gives a detailed overview of the fertilized egg model and how it is currently being used in safety assessment studies. She then describes important ways in which toxicologists and drug development programs could benefit from utilizing the fertilized egg model. This podcast is incredibly informative and is tailored to be understood and enjoyed by a broad scientific audience. Dr. Cheairs is an Assistant Professor of Pathology, Microbiology, and Immunology at New York Medical College, where she leads an innovative research program focused on using nonanimal models to study the hazardous effects of chemicals. As a result of her active involvement in teaching activities, she was appointed as Assistant Dean for PhD Programs at the Graduate School of Biomedical Sciences in 2019.

In this ToxChats© podcast, Dr. Elise Lewis provides a thorough background on the use of rabbits in DART and the future direction of their use as alternative species for other types of nonclinical safety studies. Topics include advantages and challenges, sourcing, behavior, physiology, and the practicality of rabbits, and the translatability of rabbit data to other nonclinical species and humans. Dr. Elise Lewis is currently the Principal Director of Toxicology at Charles River Laboratories and has significant experience in reproductive, developmental, and juvenile toxicology.

In this ToxChats© episode, we interview Dr. Chris Christou, Director of Preclinical Imaging and Research Laboratories at the South Australian Health and Medical Research Institute. Dr. Christou discusses the history of sheep as a preclinical species for medical device testing, novel groundbreaking neurological disease models, and the use of sheep as an alternative model in general toxicology studies. Critical regulatory standards and international guidelines are discussed to ensure successful submissions with the US Food and Drug Administration, the Australia Therapeutic Goods Administration, and the Australia New Zealand Therapeutic Products Agency.

During the COVID-19 pandemic, there was a reduction in the availability of nonhuman primates available for conducting nonclinical toxicity assessments, and as a result, the FDA released a guidance in 2022. This sparked interest in evaluating the feasibility of performing safety studies with alternative nonrodent species or other models. This podcast is the first in a series of several podcasts sponsored by ACT, in which experts in the industry are interviewed about their experiences working with these nontraditional models.

In this ACT ToxChats© episode, Dr. Shayne Gad and Samantha Gad of Gad Consulting Services host a question and answer follow-up discussion to the ACT Signature Webinar, The Role of Chemical Characterization in Biological Risk Evaluation of Medical Devices. During the first part of the podcast, they discuss diverse medical device categories for safety evaluation, explore novel aspects of biocompatibility evaluations accepted by the FDA, and address differences in safety assessments for regulatory bodies in the US and other countries. During the second part of the podcast, they provide career advice for ACT colleagues interested in transitioning from the pharmaceutical industry or academia to medical devices in toxicology.

In this ACT ToxChats© episode, Dr. Meredith Steeves and Mr. Terry Leyden share their perspectives on the current hiring landscape for toxicologist roles in industry, how to find the right fit, tips for transitioning from a bench-based position, and how to prepare for and successfully navigate the interview and negotiation process. Dr. Steeves and Mr. Leyden have complementary roles in the hiring process for toxicologists in the biopharmaceutical industry. Dr. Steeves is a Senior Director of Toxicology and hiring manager at Eli Lilly and Mr. Leyden is a Certified Personnel Consultant and President of The Leyden Group, a Colorado-based professional recruiting and search firm. This podcast is of interest for toxicologists at all career stages, with a specific focus on trainees and early career professionals and is presented by the ACT Early Career Professional Subcommittee.

In this new ACT ToxChats© episode, Dr. Jeffrey Foy, Vice President of Toxicology at Pepgen and Dr. Scott Henry, Vice President of Nonclinical Development at Ionis Pharmaceuticals are interviewed. Drs. Foy and Henry discuss the past, present, and future of oligonucleotides. Their focus is discussing the development and challenges that oligonucleotides face as a class of drugs.

One of the most common misconceptions about the opioid crisis is that it only affects people with a long history of drug abuse. Today, more than ever, a more diverse population is affected, potentially due to illicit fentanyl on the black market. In this ACT ToxChats© podcast, joined by Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, we discuss the history of opioid abuse, the factors that might have contributed to the current crisis, and other drugs that have played a role. We also discuss ways pharmaceutical and regulatory toxicologists may intervene.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), Multisystem Inflammatory Syndrome in Children (MIS-C), Adults (MIS-A), Neonates (MIS-N), and some Vaccinees (MIS-V). These are all considered clinically distinct diseases; however, the MIS-X diseases have overlapping symptoms and treatments with Kawasaki Disease (KD). MIS-C, MIS-A, MIS-N, and KD occur with increased frequencies several weeks following increased numbers of COVID-19 and for KD other pathogens. The incidence rate for MIS-C, MIS-A, MIS-N, and KD are typically a factor of roughly 5,000 lower than COVID-19 and for KD other pathogens. In this podcast, Dr. Darrell Ricke advances the hypothesis that MIS-C, MIS-A, MIS-N, MIS-V, and KD all represent a novel type of antibody-dependent enhanced (ADE) diseases associated with hyperactivation of granulocytes or mast cells. Symptoms for these diseases overlap those of histamine intolerance (HIT) coupled with pathogen associated symptoms. This ADE model proposes that antibody titer levels higher than primary immune response levels can hyperactivate granulocytes or mast cells to release inflammatory molecules including histamine; MIS-X and KD disease symptoms onset when histamine levels exceed the individual’s tolerance level. The proposed ADE model purports that patient treatment with intravenous immunoglobulin (IVIG) is successful in treating the MIS-X disease because IVIG compete with pathogen antibodies for binding to Fc receptors on immune cells, thereby reducing the immune responses to the pathogen or vaccine protein. This model is further supported with the vaccine spike protein activating immune cells via envisioned Fc receptor binding. This ADE model proposes additional antihistamine and diamine oxidase (DAO) adjunctive treatments combined with current standard of care treatments for investigation.

The severity of COVID-19 varies by individual spanning from asymptomatic, mild, moderate, severe, critical, and chronic disease. Prior to the availability of vaccines, high antibody titers correlated with disease severity. This was also observed for SARS disease. These high antibody titers on initial infections result from memory B cell responses with cross-reactive antibody responses from previous infection of likely other betacoronavirus family members. In general, family members of the betacoronavirus family leverage Fc receptor antibody uptake of viruses by phagocytic cells to infect these innate immune cells. This extended cellular tropism of phagocytic immune cells is dependent upon Fc receptors and antibodies. It is hypothesized that SARS-CoV-2 with higher antibody titers can infect phagocytic immune cells; SARS-CoV-2 infection of these cells has been observed in some patients with severe COVID-19. This proposed antibody-dependent enhancement (ADE) of disease has been proposed to a key transition of infection from respiratory infection to multi-organ disease in some severe COVID-19 patients. While the main medical community believes that there is no ADE associated with SARS-CoV-2 infections, multiple clinical studies are consistent with SARS-CoV-2 infection of monocytes and macrophages in some severe COVID-19 patients. The podcast discusses data available in the summer of 2022.