Peer reviewed publications featuring Vium.
Development of the Digital Arthritis Index, a Novel Metric to Measure Disease Parameters in a Rat Model of Rheumatoid Arthritis
Abstract: Despite a broad spectrum of anti-arthritic drugs currently on the market, there is a constant demand to develop improved therapeutic agents. Efficient compound screening and rapid evaluation of treatment efficacy in animal models of rheumatoid arthritis (RA) can accelerate the development of clinical candidates. Compound screening by evaluation of disease phenotypes in animal models facilitates preclinical research by enhancing understanding of human pathophysiology; however, there is still a continuous need to improve methods for evaluating disease. Current clinical assessment methods are challenged by the subjective nature of scoring-based methods, time-consuming longitudinal experiments, and the requirement for better functional readouts with relevance to human disease. To address these needs, we developed a low-touch, digital platform for phenotyping preclinical rodent models of disease. As a proof-of-concept, we utilized the rat collagen-induced arthritis (CIA) model of RA and developed the Digital Arthritis Index (DAI), an objective and automated behavioral metric that does not require human-animal interaction during the measurement and calculation of disease parameters. The DAI detected the development of arthritis similar to standard in vivo methods, including ankle joint measurements and arthritis scores, as well as demonstrated a positive correlation to ankle joint histopathology. The DAI also determined responses to multiple standard-of-care (SOC) treatments and nine repurposed compounds predicted by the SMarTRTM Engine to have varying degrees of impact on RA. The disease profiles generated by the DAI complemented those generated by standard methods. The DAI is a highly reproducible and automated approach that can be used in-conjunction with standard methods for detecting RA disease progression and conducting phenotypic drug screens.
Circulating microRNA and automated motion analysis as novel methods of assessing chemotherapy-induced peripheral neuropathy in mice
Chemotherapy-induced peripheral neuropathy (CiPN) is a serious adverse effect in the clinic, but nonclinical assessment methods in animal studies are limited to labor intensive behavioral tests or semi-quantitative microscopic evaluation. Hence, microRNA (miRNA) biomarkers and automated in-life behavioral tracking were assessed for their utility as non-invasive methods. To address the lack of diagnostic biomarkers, we explored miR-124, miR-183 and miR-338 in a CiPN model induced by paclitaxel, a well-known neurotoxic agent. In addition, conventional and Vium’s innovative Digital Vivarium technology-based in-life behavioral tests and postmortem microscopic examination of the dorsal root ganglion (DRG) and the sciatic nerve were performed. Terminal blood was collected on days 8 or 16, after 20 mg/kg paclitaxel was administered every other day for total of 4 or 7 doses, respectively, for plasma miRNA quantification by RT-qPCR. DRG and sciatic nerve samples were collected from mice sacrificed on day 16 for miRNA quantification. Among the three miRNAs analyzed, only miR-124 was statistically significantly increased (5 fold and 10 fold on day 8 and day 16, respectively). The increase in circulating miR-124 correlated with cold allodynia and axonal degeneration in both DRG and sciatic nerve. Automated home cage motion analysis revealed for the first time that nighttime motion was significantly decreased (P < 0.05) in paclitaxel-dosed animals. Although both increase in circulating miR-124 and decrease in nighttime motion are compelling, our results provide positive evidence warranting further testing using additional peripheral nerve toxicants and diverse experimental CiPN models.
Retrospective Analysis of the Effects of Identification Procedures and Cage Changing by Using Data from Automated, Continuous Monitoring
Abstract: Many variables can influence animal behavior and physiology, potentially affecting scientific study outcomes. Laboratory and husbandry procedures-including handling, cage cleaning, injections, blood collection, and animal identification-may produce a multitude of effects. Previous studies have examined the effects of such procedures by making behavioral and physiologic measurements at specific time points; this approach can be disruptive and limits the frequency or duration of observations. Because these procedures can have both acute and long-term effects, the behavior and physiology of animals should be monitored continuously. We performed a retrospective data analysis on the effects of 2 routine procedures, animal identification and cage changing, on motion and breathing rates of mice continuously monitored in the home cage. Animal identification, specifically tail tattooing and ear tagging, as well as cage changing, produced distinct and reproducible postprocedural changes in spontaneous motion and breathing rate patterns. Behavioral and physiologic changes lasted approximately2 d after tattooing or ear tagging and 2 to 4 d for cage changing. Furthermore, cage changes showed strain-, sex-,and time-of-day-dependent responses but not age-dependent differences. Finally, by reviewing data from a rodent model of multiple sclerosis as a retrospective case study, we documented that cage changing inadvertently affected experimental outcomes.In summary, we demonstrate how retrospective analysis of data collected continuously can provide high-throughput,meaningful, and longitudinal insights in to how animals respond to routine procedures.
Lim et al., (2019) J Am Assoc Lab Anim Sci epub. Contact Us to request a copy of this article.
Mouse Model of Liver Toxicity
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We hypothesize that continuous monitoring of behavioral and physiological parameters will provide clinically relevant data to assess disease in induction rodent models, including the Con A- induced mouse model of liver disease. The objective of this study was to evaluate behavioral and physiological characteristics of Con A-induced mice using different doses of Con A.
MRL/lpr Model of Systemic Lupus Erythematosus
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We hypothesize that continuous monitoring of behavioral and physiological parameters will provide additional meaningful data to assess disease and efficacy in genetic rodent models of disease, including SLE. To address this hypothesis, the objectives of this study were: 1) To investigate behavioral and physiological characteristics of MRL/lpr mice using a low-touch, continuous monitoring platform, and 2) To evaluate and compare the effects of standard of care (SOC) compounds on conventional disease measures as well as behavioral and physiological phenotypes in MRL/lpr mice.
Paraquat Model of Lung Injury
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Current challenges provide opportunities to develop low- touch, automated, in-life methods to assess pulmonary function and lung edema in rodents. We hypothesize that Vium’s automated Digital Biomarkers, specifically Breathing Rate, will provide physiologically relevant data to assess respiratory disease progression in a PQ-induced rat model of lung injury.
Phenotying Mouse Models
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The rapid growth of systems biology approaches in preclinical research, such as whole-genome sequencing and genome editing, has contributed to the need for high-throughput and reproducible phenotypic screening of genetically engineered animals. The relationship between genotype and phenotype is complex: targeted genes of interest interact with background genes and unknown mutations, as well as epigenetic and environmental factors, to exert specific or collective effects on health and behavior.
Bleomycin Model of Pulmonary Fibrosis
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Here we demonstrate how Vium’s platform can be used to monitor respiratory disease progression in a bleomycin mouse model of ideopathic pulmonary fibrosis (IPF). Vium’s automated Breathing Rate showed strong and distinct changes as early as three days post-induction until close to study end. Although further investigation is required to assess the underlying disease mechanisms, initial evidence suggests reduced breathing rates early in disease may reflect the acute inflammatory phase and elevated breathing rates later in disease may reflect the chronic fibrotic phase of disease, generally characterizing this model.
Pseudomonas aeruginosa Model of Lung Infection
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Here we demonstrate how Vium’s platform can be used to monitor respiratory disease progression in a Pseudomonas aeruginosa (PA01)-induced mouse model of lung infection. Vium’s Digital Biomarkers, specifically automated Breathing Rate, showed changes as early as eight hours post-infection, and these changes persisted until close to study end. The advantage of using a continuous monitoring platform to evaluate breathing rates in the home cage is the ability to observe animals in their natural behavioral states across longer periods of time, which may lead to more sensitive and consistent data collection.
Featured: Gene Therapy Efficacy Assessment in Batten Mice Using the Vium Digital Vivarium
Developed in conjunction with the University of Pennsylvania Perelman School of Medicine.
CLN2 disease, a form of Batten disease, is a neurodegenerative lysosomal storage disorder caused by mutations in the gene encoding the soluble enzyme tripeptidyl- peptidase-1 (TPP1). This model recapitulates most features of the human disease such as shortened lifespan, seizures, or abnormal gait. Monitoring of the neurobehavioral function in this model is challenging, however, as they are prone to noise- or stress-induced fatal seizures when handled. Real time non-invasive continuous monitoring using smart cages (Vium, Inc.) allows sensitive and non-biased recording of disease phenotype and treatment-related rescue in a seizure-prone mouse model, while limiting handling-related deaths.
Presented at AALAS National Meeting 2018
Presented at AALAS National Meeting 2018
Presented at Immunology 2018
Presented at Immunology 2016
Presented at the AALAS NCB Annual Symposium
In Conjunction with UPenn
Presented at Neuroscience 2016
Presented at World Preclinical Congress 2017