E-Textiles for Sports and Fitness Sensing: Current State, Challenges, and Future Opportunities.

E-textiles have emerged as a fast-growing area in wearable technology for sports and fitness due to the soft and comfortable nature of textile materials and the capability for smart functionality to be integrated into familiar sports clothing. This review paper presents the roles of wearable technologies in sport and fitness in monitoring movement and biosignals used to assess performance, reduce injury risk, and motivate training/exercise. The drivers of research in e-textiles are discussed after reviewing existing non-textile and textile-based commercial wearable products. Different sensing components/materials (e.g., inertial measurement units, electrodes for biosignals, piezoresistive sensors), manufacturing processes, and their applications in sports and fitness published in the literature were reviewed and discussed. Finally, the paper presents the current challenges of e-textiles to achieve practical applications at scale and future perspectives in e-textiles research and development.

AAV-RPGR Gene Therapy Rescues Opsin Mislocalisation in a Human Retinal Organoid Model of RPGR-Associated X-Linked Retinitis Pigmentosa.

Variants within the Retinitis Pigmentosa GTPase regulator (RPGR) gene are the predominant cause of X-Linked Retinitis Pigmentosa (XLRP), a common and severe form of inherited retinal disease. XLRP is characterised by the progressive degeneration and loss of photoreceptors, leading to visual loss and, ultimately, bilateral blindness. Unfortunately, there are no effective approved treatments for RPGR-associated XLRP. We sought to investigate the efficacy of RPGRORF15 gene supplementation using a clinically relevant construct in human RPGR-deficient retinal organoids (ROs). Isogenic RPGR knockout (KO)-induced pluripotent stem cells (IPSCs) were generated using established CRISPR/Cas9 gene editing methods targeting RPGR. RPGR-KO and isogenic wild-type IPSCs were differentiated into ROs and utilised to test the adeno associated virus (AAV) RPGR (AAV-RPGR) clinical vector construct. The transduction of RPGR-KO ROs using AAV-RPGR successfully restored RPGR mRNA and protein expression and localisation to the photoreceptor connecting cilium in rod and cone photoreceptors. Vector-derived RPGR demonstrated equivalent levels of glutamylation to WT ROs. In addition, treatment with AAV-RPGR restored rhodopsin localisation within RPGR-KO ROs, reducing mislocalisation to the photoreceptor outer nuclear layer. These data provide mechanistic insights into RPGRORF15 gene supplementation functional potency in human photoreceptor cells and support the previously reported Phase I/II trial positive results using this vector construct in patients with RPGR-associated XLRP, which is currently being tested in a Phase III clinical trial.

A Review of the Validity and Reliability of Accelerometer-Based Metrics From Upper Back-Mounted GNSS Player Tracking Systems for Athlete Training Load Monitoring.

ABSTRACT: Dawson, L, Beato, M, Devereux, G, and McErlain-Naylor, SA. A review of the validity and reliability of accelerometer-based metrics from upper back-mounted GNSS player tracking systems for athlete training load monitoring. J Strength Cond Res 38(8): e460-e475, 2024-Athlete load monitoring using upper back-mounted global navigation satellite system (GNSS) player tracking is common within many team sports. However, accelerometer-based load monitoring may provide information that cannot be achieved with GNSS alone. This review focuses on the accelerometer-based metrics quantifying the accumulation of accelerations as an estimation of athlete training load, appraising the validity and reliability of accelerometer use in upper back-mounted GNSS player tracking systems, the accelerometer-based metrics, and their potential for application within athlete monitoring. Reliability of GNSS-housed accelerometers and accelerometer-based metrics are dependent on the equipment model, signal processing methods, and the activity being monitored. Furthermore, GNSS unit placement on the upper back may be suboptimal for accelerometer-based estimation of mechanical load. Because there are currently no feasible gold standard comparisons for field-based whole-body biomechanical load, the validity of accelerometer-based load metrics has largely been considered in relation to other measures of training load and exercise intensity. In terms of convergent validity, accelerometer-based metrics (e.g., PlayerLoad, Dynamic Stress Load, Body Load) have correlated, albeit with varying magnitudes and certainty, with measures of internal physiological load, exercise intensity, total distance, collisions and impacts, fatigue, and injury risk and incidence. Currently, comparisons of these metrics should not be made between athletes because of mass or technique differences or between manufacturers because of processing variations. Notable areas for further study include the associations between accelerometer-based metrics and other parts of biomechanical load-adaptation pathways of interest, such as internal biomechanical loads or methods of manipulating these metrics through effective training design.

Practitioner Usage, Applications, and Understanding of Wearable GPS and Accelerometer Technology in Team Sports.

ABSTRACT: Dawson, L, McErlain-Naylor, SA, Devereux, G, and Beato, M. Practitioner usage, applications, and understanding of wearable GPS and accelerometer technology in team sports. J Strength Cond Res 38(7): e373-e382, 2024-Monitoring training load is essential for optimizing the performance of athletes, allowing practitioners to assess training programs, monitor athlete progress, and minimize the risk of injury and overtraining. However, there is no universal method for training load monitoring, and the adoption of wearable global positioning system (GPS) and accelerometer technology in team sports has increased the volume of data and, therefore, the number of possible approaches. This survey investigated the usage, applications, and understanding of this technology by team sports practitioners. Seventy-two practitioners involved in team and athlete performance monitoring using GPS and accelerometer technology completed the survey. All respondents reported supporting the use of GPS technology in their sport, with 70.8% feeling that GPS technology is important for success. Results showed that 87.5% of respondents use data from wearable technology to inform training prescription, although only 50% use the data to influence decisions in competition. In addition, results showed that GPS metrics are used more than accelerometer-derived metrics; however, both are used regularly. Discrepancies in accelerometer usage highlighted concerns about practitioners' understanding of accelerometer-derived metrics. This survey gained insight into usage, application, understanding, practitioner needs, and concerns and criticisms surrounding the use of GPS and accelerometer metrics for athlete load monitoring. Such information can be used to improve the implementation of this technology in team sport monitoring and highlight gaps in the literature that will help to design future studies to support practitioner needs.

Consensus on a netball video analysis framework of descriptors and definitions by the netball video analysis consensus group.

Using an expert consensus-based approach, a netball video analysis consensus (NVAC) group of researchers and practitioners was formed to develop a video analysis framework of descriptors and definitions of physical, technical and contextual aspects for netball research. The framework aims to improve the consistency of language used within netball investigations. It also aims to guide injury mechanism reporting and identification of injury risk factors. The development of the framework involved a systematic review of the literature and a Delphi process. In conjunction with commercially used descriptors and definitions, 19 studies were used to create the initial framework of key descriptors and definitions in netball. In a two round Delphi method consensus, each expert rated their level of agreement with each of the descriptors and associated definition on a 5-point Likert scale (1-strongly disagree; 2-somewhat disagree; 3-neither agree nor disagree; 4-somewhat agree; 5-strongly agree). The median (IQR) rating of agreement was 5.0 (0.0), 5.0 (0.0) and 5.0 (0.0) for physical, technical and contextual aspects, respectively. The NVAC group recommends usage of the framework when conducting video analysis research in netball. The use of descriptors and definitions will be determined by the nature of the work and can be combined to incorporate further movements and actions used in netball. The framework can be linked with additional data, such as injury surveillance and microtechnology data.

The Influence of Geographical Origin, Age, Sex, and Animal Husbandry on the Spontaneous Histopathology of Laboratory Cynomolgus Macaques (Macaca Fascicularis): A Contemporary Global and Multisite Review of Historical Control Data.

To investigate the influence of geographical origin, age, and sex on toxicologically relevant spontaneous histopathology findings in cynomolgus macaques (Macaca fascicularis), we performed a comparative analysis of historical control data (HCD) from 13 test sites that included 3351 animals (1645 females and 1706 males) sourced from Mauritius, China, Vietnam, and Cambodia, aged from 2 to 9.5 years, and from 446 toxicology studies evaluated between 2016 and 2021. The most common findings were mononuclear infiltrates in the kidney, liver, brain, and lung, which showed highest incidences in Mauritian macaques, and heart, salivary glands, and gastrointestinal tract (GIT), which showed highest incidences of mononuclear infiltrates in mainland Asian macaques. Developmental and degenerative findings were more common in Mauritian macaques, while lymphoid hyperplasia and lung pigment showed higher incidences in Asian macaques. Various sex and age-related differences were also present. Despite origin-related differences, the similarities in the nature and distribution of background lesions indicate that macaques from all geographical regions are suitable for toxicity testing and show comparable lesion spectrum. However, in a toxicity study, it is strongly recommended to use animals from a single geographical origin and to follow published guidelines when using HCD to evaluate and interpretate commonly diagnosed spontaneous lesions.

The effects of bowling lines and lengths on the spatial distribution of successful power-hitting strokes in international men's one-day and T20 cricket.

This study examined 503 power-hitting strokes that resulted in the maximum of 6-runs being scored in international men's one-day and T20 cricket. Chi-Squared analyses were conducted to determine if performance and situational variables were associated with the distribution (direction) of aerial power-hitting strokes. Results revealed that bowling length, bowling line, bowler type and powerplays were all significantly (p < 0.001) associated with ball-hitting distribution. Post-hoc analysis of the standardised residuals revealed that greater than expected 6's were scored behind square and were associated with short-pitched bowling, fast bowling and the power-play. Similarly, bowling the half-volley length and the outside off line resulted in greater than expected 6's on the off-side. The results suggest that bowlers should try to avoid offering width outside the off stump as well as bowling the half-volley and short-pitched lengths as these bowling lines and lengths present batters with greater opportunities to score maximum runs. Fast bowling is revealed to be more susceptible to power-hitting strokes than spin bowling. Conversely, batters may wish to target the areas behind square or on the off-side for opportunities to score maximum runs, and they should look to take full advantage of the powerplay field restrictions.

Comparing biomechanical time series data across countermovement shrug loads.

The effect of load on time-series data has yet to be investigated during weightlifting derivatives. This study compared the effect of load on the force-time and velocity-time curves during the countermovement shrug (CMS). Twenty-nine males performed the CMS at relative loads of 40%, 60%, 80%, 100%, 120%, and 140% one repetition maximum (1RM) power clean (PC). A force plate measured the vertical ground reaction force (VGRF), which was used to calculate the barbell-lifter system velocity. Time-series data were normalized to 100% of the movement duration and assessed via statistical parametric mapping (SPM). SPM analysis showed greater negative velocity at heavier loads early in the unweighting phase (12-38% of the movement), and greater positive velocity at lower loads during the last 16% of the movement. Relative loads of 40% 1RM PC maximised propulsion velocity, whilst 140% 1RM maximized force. At higher loads, the braking and propulsive phases commence at an earlier percentage of the time-normalized movement, and the total absolute durations increase with load. It may be more appropriate to prescribe the CMS during a maximal strength mesocycle given the ability to use supramaximal loads. Future research should assess training at different loads on the effects of performance.

Perception and application of flywheel training by professional soccer practitioners.

Growing evidence supports use of eccentric methods for strength development and injury prevention within elite soccer, yet uncertainty remains regarding practitioners' application of flywheel (isoinertial) methods. The aims of this study were to investigate how the flywheel training literature is perceived and applied by elite soccer practitioners, highlight gaps in knowledge and develop industry-relevant research questions. Fifty-one practitioners completed an electronic questionnaire. Fourteen Likert scale statements were grouped into topics: strength and performance; post-activation performance enhancement and methodological considerations; chronic strength; chronic performance; injury prevention. Three general questions followed, allowing more detail about flywheel training application. A Majority of the participants reported ≥ 2 years' experience of programming flywheel training. Nearly all participants agreed that familiarisation is needed. Practitioners agree that flywheel training can improve sport performance, strength and likelihood of non-contact injury outcomes. Most practitioners prescribe 2 weekly sessions during pre- and in-season periods. Flywheel sessions mostly consist of squats but a variety of exercises (lunge, hip hinge, and open kinetic chain) are also frequently included. Practitioners are mostly unsure about differences between flywheel and traditional resistance training equipment and outcomes, practicality of flywheel equipment, and evidence-based guidelines. The investigation provides valuable insight into the perspectives and application of flywheel training within elite soccer, highlighting its perceived efficacy for strength and injury prevention.

Proof of Concept: The Use of Whole-Slide Images (WSI) for Peer Review of Tissues on Routine Regulatory Toxicology Studies.

This Proof of Concept (POC) study was to assess whether assessment of whole slide images (WSI) of the 2 target tissues for a contemporaneous peer review can elicit concordant results to the findings generated by the Study Pathologist from the glass slides. Well-focused WSI of liver and spleen from 4 groups of mice, that had previously been diagnosed to be the target tissues by an experienced veterinary toxicologic pathologist examining glass slides, were independently reviewed by 3 veterinary pathologists with varying experience in assessment of WSIs. Diagnostic discrepancies were then reviewed by an experienced adjudicating pathologist. Assessment of microscopic findings using WSI showed concordance with the glass slides, with only slight discrepancy in severity grades noted. None of the lesions recorded by the Study pathologist were "missed" and no lesions were added by the pathologists evaluating WSIs, thus demonstrating equivalence of the WSI to glass slides for this study.

Multisite Analysis of Lesions in the Respiratory Tract of the Rat and Nonhuman Primate (Cynomolgus Monkey) Exposed to Air, Vehicle, and Inhaled Small Molecule Compounds.

This paper presents a review of the nature, range, and incidences of background pathology findings in the respiratory tract of cynomolgus monkeys and rats. Data were collected from 81 inhalation studies and 133 non-inhalation studies evaluated at 3 geographically distinct contract research organization facilities. The inhalation studies were comprised of 44 different small molecule pharmaceuticals or chemicals which were also analyzed in order to understand the patterns of induced changes within the respiratory tract. The lung was the most frequently affected organ in both species, with increased alveolar macrophages being the most common background and test article-related finding. In the upper respiratory tract (URT), inflammatory cell infiltrates were the most common background findings in the nasal cavity in monkeys. Induced URT findings were more frequent in rats than monkeys, with squamous metaplasia in the larynx, and goblet cell hyperplasia in the nasal cavity being the most common. Overall, the data revealed a limited pattern of response to inhaled molecules in the respiratory tract, with background and test article-related findings often occurring in the same regions. It is hoped that these data will assist in the interpretation of findings in the respiratory tract induced by novel inhaled small molecule entities.

BSTP Review of 12 Case Studies Discussing the Challenges, Pathology, Immunogenicity, and Mechanisms of Inhaled Biologics.

The inhalation route is a relatively novel drug delivery route for biotherapeutics and, as a result, there is a paucity of published data and experience within the toxicology/pathology community. In recent years, findings arising in toxicology studies with inhaled biologics have provoked concern and regulatory challenges due, in part, to the lack of understanding of the expected pathology, mechanisms, and adversity induced by this mode of delivery. In this manuscript, the authors describe 12 case studies, comprising 18 toxicology studies, using a range of inhaled biotherapeutics (monoclonal antibodies, fragment antigen-binding antibodies, domain antibodies, therapeutic proteins/peptides, and an oligonucleotide) in rodents, nonhuman primates (NHPs), and the rabbit in subacute (1 week) to chronic (26 weeks) toxicology studies. Analysis of the data revealed that many of these molecules were associated with a characteristic pattern of toxicity with high levels of immunogenicity. Microscopic changes in the airways consisted of a predominantly lymphoid perivascular/peribronchiolar (PV/PB) mononuclear inflammatory cell (MIC) infiltrate, whereas changes in the terminal airways/alveoli were characterized by simple ("uncomplicated") increases in macrophages or inflammatory cell infiltrates ranging from mixed inflammatory cell infiltration to inflammation. The PV/PB MIC changes were considered most likely secondary to immunogenicity, whereas simple increases in alveolar macrophages were most likely secondary to clearance mechanisms. Alveolar inflammatory cell infiltrates and inflammation were likely induced by immune modulation or stimulation through pharmacologic effects on target biology or type III hypersensitivity (immune complex disease). Finally, a group of experts provide introductory thoughts regarding the adversity of inhaled biotherapeutics and the basis for reasonable differences of opinion that might arise between toxicologists, pathologists, and regulators.

Concentric and eccentric inertia-velocity and inertia-power relationships in the flywheel squat.

The aim of this study was to evaluate the effects of varying flywheel inertia on velocity and power during flywheel squats. Fifteen healthy physically active males performed 6 maximal effort flywheel half-squats at each of 0.029, 0.061, 0.089 and 0.121 kg·m2, with velocity recorded via 3D motion capture and power recorded via inbuilt transducer. Peak concentric velocity (χ2 = 37.9; p < 0.001), peak eccentric velocity (χ2 = 24.9; p < 0.001), mean concentric velocity (F(3) = 52.7; p < 0.001) and mean eccentric velocity (χ2 = 16.8; p < 0.001) all tended to decrease with increases in flywheel inertia, whereas the ratio of peak eccentric to peak concentric power (F(3) = 4.26; p = 0.010) tended to increase. Flywheel inertia had no significant effect on peak concentric or eccentric power, or the ratio of eccentric to concentric peak or mean velocities. The best fit subject-specific inertia-velocity relationships were reported for peak concentric velocity (median linear R2 = 0.95, median logarithmic R2 = 0.97). The results suggest that velocity, rather than power, should be used to prescribe and monitor flywheel squat exercise intensities, and that individualized linear relationships between inertia and peak concentric velocity can be used for this purpose.

Inter-unit reliability of IMU Step metrics using IMeasureU Blue Trident inertial measurement units for running-based team sport tasks.

The aim of this study was to determine the inter-unit reliability of IMU Step biomechanical load monitoring metrics using IMeasureU Blue Trident inertial measurement units in tasks common to running-based team sports. Knowledge of variability between units is required before researchers and practitioners can make informed decisions on "true" differences between limbs. Sixteen male college soccer players performed five running-based tasks, generating 224 trials and 17,012 steps. Data were analysed for each task and for the whole session, investigating six IMU Step metrics: step count; impact load; bone stimulus; and low, medium and high intensity steps. Inter-unit reliability was excellent (ICC ≥ 0.90) for 21 out of 26 metrics, and good (0.83 ≤ ICC ≤ 0.86) for all other metrics except for Yo-Yo impact load (ICC = 0.79) which was acceptable. These findings confirm the inter-unit reliability of IMU Step metrics using IMeasureU Blue Trident inertial measurement units for running-based team sports. Now that inter-unit variability has been quantified, researchers and practitioners can use this information when interpreting inter-limb differences for monitoring external biomechanical training load.

Comparing power hitting kinematics between skilled male and female cricket batters.

Organismic, task, and environmental constraints are known to differ between skilled male and female cricket batters during power hitting tasks. Despite these influences, the techniques used in such tasks have only been investigated in male cricket batters. This study compared power hitting kinematics between 15 male and 15 female batters ranging from university to international standard. General linear models were used to assess the effect of gender on kinematic parameters describing technique, with height and body mass as covariates. Male batters generated greater maximum bat speeds, ball launch speeds, and ball carry distances than female batters on average. Male batters had greater pelvis-thorax separation in the transverse plane at the commencement of the downswing (ß = 1.14; p = 0.030) and extended their lead elbows more during the downswing (ß = 1.28; p = 0.008) compared to female batters. The hypothesised effect of gender on the magnitude of wrist uncocking during the downswing was not observed (ß = -0.14; p = 0.819). The causes of these differences are likely to be multi-factorial, involving aspects relating to the individual players, their history of training experiences and coaching practices, and the task of power hitting in male or female cricket.

Effect of Postactivation Potentiation After Medium vs. High Inertia Eccentric Overload Exercise on Standing Long Jump, Countermovement Jump, and Change of Direction Performance.

ABSTRACT: Beato, M, De Keijzer, KL, Leskauskas, Z, Allen, WJ, Dello Iacono, A, and McErlain-Naylor, SA. Effect of postactivation potentiation after medium vs. high inertia eccentric overload exercise on standing long jump, countermovement jump, and change of direction performance. J Strength Cond Res 35(9): 2616-2621, 2021-This study aimed to evaluate the postactivation potentiation (PAP) effects of an eccentric overload (EOL) exercise on vertical and horizontal jumps and change of direction (COD) performance. Twelve healthy physically active male subjects were involved in a crossover study. The subjects performed 3 sets of 6 repetitions of EOL half squats for maximal power using a flywheel ergometer. Postactivation potentiation using an EOL exercise was compared between a medium (M-EOL) vs. high inertia (H-EOL) experimental condition. Long jump (LJ) was recorded at 30 seconds, 3, and 6 minutes after both EOL exercises and compared with baseline values (control). The same procedure was used to assess countermovement jump (CMJ) height and peak power and 5-m COD test (COD-5m). A fully Bayesian statistical approach to provide probabilistic statements was used in this study. Long jump performance reported improvements after M-EOL and H-EOL exercise (Bayes factor [BF10] = 32.7, strong; BF10 = 9.2, moderate), respectively. Countermovement jump height (BF10 = 135.6, extreme; BF10 > 200, extreme), CMJ peak power (BF10 > 200, extreme; BF10 = 56.1, very strong), and COD-5m (BF10 = 55.7, very strong; BF10 = 16.4, strong) reported improvements after M-EOL and H-EOL exercise, respectively. Between analysis did not report meaningful differences in performance between M-EOL and H-EOL exercises. The present outcomes highlight that PAP using an EOL (M-EOL and H-EOL) improves LJ, CMJ height, CMJ peak power, and COD-5m in male athletes. The optimal time window for the PAP effect was found for both EOL conditions from 3 to 6 minutes. However, M-EOL and H-EOL produce similar PAP effect on LJ, CMJ, and COD-5m tasks.

Physical, physiological, and technical demands of national netball umpires at different competition levels.

To compare demands of national netball umpires between levels of competition, 22 Netball New Zealand high-performance umpires participated in this investigation. These included from highest to lowest standard: 9 × semi-professional ANZ Championships (ANZC); 6 × National A Squad (NZA); and 7 × National Development Squad (DEV). Physical (global positioning system tri-axial accelerometry), physiological (heart rate) and technical (video analysis) demands were determined for 48 (16 per group) umpire match performances. Level of competition had no significant effect on physical or mean physiological demands. However, ANZC umpires spent a lower proportion of time at low heart rates compared to DEV, and a greater proportion of time at high, rather than moderate, heart rates compared to NZA. Compared to lower standard umpires, ANZC spent lesser proportions of time standing but greater proportions of time walking backwards and sideways, and turning to change direction. Furthermore, ANZC umpires spent lower proportions of time jogging, but greater proportions of time sprinting compared to DEV. Finally, ANZC umpires spent longer mean durations than DEV on the goal third side line. As such, the difference in demands experienced by national netball umpires between levels of competition is more technical than physical or physiological.

Effect of racket-shuttlecock impact location on shot outcome for badminton smashes by elite players.

A logarithmic curve fitting methodology for the calculation of badminton racket-shuttlecock impact locations from three-dimensional motion capture data was presented and validated. Median absolute differences between calculated and measured impact locations were 3.6 [IQR: 4.4] and 3.5 [IQR: 3.5] mm mediolaterally and longitudinally on the racket face, respectively. Three-dimensional kinematic data of racket and shuttlecock were recorded for 2386 smashes performed by 65 international badminton players, with racket-shuttlecock impact location assessed against instantaneous post-impact shuttlecock speed and direction. Mediolateral and longitudinal impact locations explained 26.2% (quadratic regression; 95% credible interval: 23.1%, 29.2%; BF10 = 1.3 × 10131, extreme; p < 0.001) of the variation in participant-specific shuttlecock speed. A meaningful (BF10 = ∞, extreme; p < 0.001) linear relationship was observed between mediolateral impact location and shuttlecock horizontal direction relative to a line normal to the racket face at impact. Impact locations within one standard deviation of the pooled mean impact location predict reductions in post-impact shuttlecock speeds of up to 5.3% of the player's maximal speed and deviations in the horizontal direction of up to 2.9° relative to a line normal to the racket face. These results highlight the margin for error available to elite badminton players during the smash.

Experiences of Undergraduates Publishing Biomechanics Research.

The aim of this study was to investigate student experiences of publishing undergraduate research in biomechanics. A total of 29 former students with experience of publishing peer-reviewed undergraduate biomechanics research completed an online survey regarding their perceived benefits, level of involvement, and experiences in aspects of the research process. On average, students perceived their experiences to be "largely helpful" or greater in all aspects. Areas were identified corresponding to: the greatest perceived benefits (eg, understanding of the research process); the least perceived benefits (eg, statistical analysis skills); the greatest student involvement (eg, reading relevant literature); and the least student involvement (eg, developing hypotheses and/or methods). A thematic analysis of open question responses identified themes relating to: future career, skills, scientific process, intra- and interpersonal factors, and pedagogy. Common intended learning outcomes may be achieved through involvement in the research process independently of the level of staff involvement. Staff should be encouraged to involve students in publishable biomechanics research projects where this is possible without compromising research standards and should explore ways of recreating the publishing process internally for all students.

Histopathological Findings in Cynomolgus Macaques ( Macaca fascicularis) Consistent with Secondary Immunological Reaction to Biotherapeutics with an Emphasis on the CNS and Eye.

Biotherapeutics are pharmaceutical products derived from or synthesized by biological systems. Such molecules carry the potential for immunogenicity which may lead to adverse immune responses. The cynomolgus macaque ( Macaca fascicularis) is the species of choice in nonclinical safety assessment of biotherapeutics. The main aim of this study was to confirm whether mononuclear cell infiltrates at specific locations represent a generic effect of biotherapeutics, and therefore the result of their immunogenicity. Following a review of microscopic findings in studies conducted over a 10-year period at one test facility, 15% of biotherapeutics were reported to have such findings. The most commonly affected site was the choroid plexus and less frequently the meninges and ciliary body. The reporting of such findings as test article-related becomes more subjective as the severity and incidence decreases. To assess the accuracy of such associations, a mathematical approach was employed to determine the probability of obtaining the observed results by chance. There was good agreement between this approach and the original findings. In addition to an increased number and size of mononuclear cell infiltrates in the brain, biotherapeutic administration was strongly associated with the presence of plasma cells and eosinophils.