Motor Performance Tests Research Articles

Secular trends of physical fitness in Austrian children attending sports schools: An analysis of repeated cross-sections from 2006 to 2023

BackgroundPhysical fitness (PF) offers numerous physical and mental health benefits, especially during childhood. Previous studies investigating trends in children's PF over the years reported contradictory findings. ObjectiveTo identify and analyse secular trends in PF among Austrian schoolchildren from 2006 to 2023. MethodA repeated cross-sections design was used to examine the PF of children enrolling in sports schools between 2006 and 2023. During this period, a standardized eight-item motor performance testing battery was administered yearly to capture markers of strength, speed, endurance, agility and reaction time in Austrian schools. ResultsA total of n = 3827 children (996 girls) with a mean age of 9.9 ± 1.0 years were included. Linear mixed models indicated significant declines in sprint performance (5, 10, 20 m), tapping, jump (long jump and drop jump), throwing (medicine ball), and agility (snake run). No changes were observed in cardiorespiratory fitness (8 min run) or reaction time. ConclusionThere has been a steady decline in PF among Austrian children attending sports schools. This finding underscores the need for enhanced PF monitoring and training in schools to improve public health outcomes.

Mouse Model of Parkinson's Disease with Bilateral Dorsal Striatum Lesion with 6-Hydroxydopamine Exhibits Cognitive Apathy-like Behavior.

Among the symptoms of Parkinson's disease (PD), apathy comprises a set of behavioral, affective, and cognitive features that can be classified into several subtypes. However, the pathophysiology and brain regions that are involved in these different apathy subtypes are still poorly characterized. We examined which subtype of apathy is elicited in a mouse model of PD with 6-hydroxydopamine (6-OHDA) lesions and the behavioral symptoms that are exhibited. Male C57/BL6J mice were allocated to sham (n = 8) and 6-OHDA (n = 13) groups and locally injected with saline or 4 µg 6-OHDA bilaterally in the dorsal striatum. We then conducted motor performance tests and apathy-related behavioral experiments. We then pathologically evaluated tyrosine hydroxylase (TH) immunostaining. The 6-OHDA group exhibited significant impairments in motor function. In the behavioral tests of apathy, significant differences were observed between the sham and 6-OHDA groups in the hole-board test and novelty-suppressed feeding test. The 6-OHDA group exhibited impairments in inanimate novel object preference, whereas social preference was maintained in the three-chamber test. The number of TH+ pixels in the caudate putamen and substantia nigra compacta was significantly reduced in the 6-OHDA group. The present mouse model of PD predominantly showed dorsal striatum dopaminergic neuronal loss and a decrease in novelty seeking as a symptom that is related to the cognitive apathy component.

RAZMERJE MED ZMOGLJIVOSTJO V MOČI IN GIBALNO ZMOGLJIVOSTJO V STOJI NA ROKAH: MODEL STROJNEGA UČENJA

The present study investigated the relationship between strength capacity and motor performance in the gymnastic handstand. The hypothesis stipulated a positive relationship between motor performance and strength capacity levels. Thirty-two university students, 16 female and 16 male (24.03 ± 4.74 years of age,) participated in the study. The handstand was assessed using the absolute error of the three angles produced by the model (video) and the three angles produced by the performer. We conducted four strength tests: explosive force, maximum right-hand grip strength, maximum left-hand grip strength, and resistance force. The machine learning model was trained using 10 of the folds and cross-validated, and a linear regression test was performed using motor performance (absolute error) and strength tests (explosive force, maximum force right-hand, maximum force left-hand, and resistance force). The results showed that the machine learning model indicated a low relationship between strength capacity and motor performance. Additionally, motor performance was not found to be related to strength capacity. The results may indicate that specific capacities and the interaction of factors such as task specificity, environment, and individual characteristics influence motor performance.

QOL-26. SYTHESIS OF THE LITERATURE REVIEW ON PHYSICAL ACTIVITY IN PEDIATRIC NEURO-ONCOLOGY

Abstract BACKGROUND Physical Activity plays a vital role in physical, social, phychological wellbeing of pediatric neuro-oncologic group. However, the researches investigating the effects of physical activity on this group have been sparse. The purpose of this study was to identify studies conducted about the effects of physical activity on this population. METHODS PRISMA statement conduct review was followed in electronic database of Journal of Neuro-oncology. Two authors (SY, MT) independently conducted systematic literature searches February 2024. Keywords/Mesh terms: “physical activity’’. Randomized controlled English clinical trials are included; Studies that were published as “review”, “protocol”, “books”, “news”, not reach full text and not related to physical activity excluded. After articles had been reached, used QUADAS-2 checklist for methodological quality. RESULTS 29 articles were identified from 1721 articles, and 2 of them (published 2014-2023) were about pediatric age group. One of them was assessment (50%), while the other one was interventional study (50%). Assessment study was measured by using Bruininks-Osteretsky Test of Motor Performance, Second Edition (BOT-2) and online surveys. Interventional study analyzed the effects of aerobic exercises of three 90-minute sessions per week for 12 consecutive weeks primarily on cortical thickness, white matter, hippocampal volume and secondarily reaction time, accuracy across tests of attention, processing speed, and short term memory. CONCLUSION This abstract provides an initial scoping review of physical activity in pediatric neuro-oncology group. It demonstrates limited range of assessments, and interventions which highlights the lack of clinical evidence in this specific area. The results raise the need for further research in this field to help the development of physical activity guidelines for evaluation and physical activity methods in children with ataxia, and tumours expecially posterior fossa brain tumors. Investigation of different physical activity methods in a group of neuro-oncology children in need of support is major importance.

Functional clinical motor performance tests to assess potential fall risks in patients with haemophilia: A case-control study.

Patients with haemophilia (PwH) are at increased risk of falls due to haemophilic arthropathy. Yet, studies on clinical tests associated with the risk of falling are scarce in PwH. (1) To evaluate the feasibility of different clinical motor performance tests associated with the risk of falling in PwH; (2) to evaluate PwH's performance of these tests compared to a control group; (3) to identify possible influencing factors that affect performance. Twenty-nine severe and moderate PwH (57.0 years, IQR: 48.0-61.5) and 29 healthy age- and BMI-matched control participants (CG) performed 13 different clinical tests (SPPB, timed up and go, push and release, functional reach, single-leg stance, knee and grip strength). Haemophilia joint health score (HJHS), kinesiophobia (TSK-11), subjective physical performance (HEP-Test-Q), falls efficiency (FES-I) and falls were assessed. No adverse events occurred. PwH showed impaired performance in all clinical tests, a lower falls efficiency and a higher HJHS than CG. PwH with higher HJHS, lower HEP-Test-Q and higher TSK-11 scores showed higher deficits. Largest discrepancies were observed in the single-leg stance with eyes open and knee extensor strength, where orthopaedically majorly affected PwH showed worse performance compared to minorly affected PwH and the CG, respectively. The prevalence of ≥1 fall in the last year was 27.6% (PwH) and 10.3% (CG). These clinical tests are feasible in PwH. Impaired joint status, a high kinesiophobia and low physical performance impair performance. These tests can be used by clinicians for gaining specific information on functional motor abilities of patients.

Prevalence and factors associated with low functional mobility in older adults.

To analyze the factors associated with low functional mobility in older adults residing in Alcobaça, BA. This is an epidemiological survey with a cross-sectional design, conducted in 2015 with 473 older adults (62.4% women; mean age 70.2 ± 8.2 years) from Alcobaça, BA. The interview script addressed sociodemographic characteristics, health, and behavioral aspects. Functional mobility was assessed using the Short Physical Performance Battery (≤6 points). Inferential analyses were conducted using the Mann-Whitney U test and Poisson regression (with robust variance and estimation of prevalence ratios and their respective 95.0% confidence intervals). The prevalence of low functional mobility was 9.6%, with associated factors including the use of alcoholic beverages (PR = 1.7, 95% CI: 1.01-1.13) and the number of repetitions in elbow flexion (PR = 1.01, 95% CI: 1.01-1.05). Additionally, older adults with low mobility had lower height, thigh circumference, and lower performance in handgrip strength tests, elbow flexion, and flexibility. They also spent more time in sedentary behavior and less time in physical activity compared to older adults with preserved mobility (p < 0.05). Older adults with low mobility exhibit poorer values in anthropometric parameters, lower performance in motor tests, spend less time engaged in physical activities, and more time in sedentary behavior.

The Effectiveness of Sensory-Motor Integration Exercises on Social Skills and Motor Performance in Children with Autism.

The current study aims to investigate the effectiveness of sensory-motor integration exercises on social skills and motor performance in children with autism spectrum disorder (ASD). This is a quasi-experimental study with a pre-test-post-test design and with a control group. The statistical population of this research included all children with ASD aged 9-11 years old in Babolsar city in 2022, among whom 30 were selected through convenient sampling from the transplant center of Babolsar, and were randomly assigned into two experimental and control groups. Then, the experimental group received the treatment program in 12 sessions. The data collection instrument included Gresham and Elliott's social skills questionnaire (Gresham FM, Elliott SN (1993) Social skills intervention guide: systematic approaches to social skills training. Spec Serv Sch 8(1):137-158) and Ulrich's motor performance test (Ulrich B, Ulrich D (1985) The role of balancing ability in performance of fundamental motor skills in 3-, 4-, and 5-year-old children. Motor Dev: Curr Select Res 1:87-97). Data analysis was conducted using covariance analysis in SPSS21. The multivariate covariance analysis test showed that there is a significant difference between the experimental and control groups in the variable of social skills and motor performance, respectively (P < 0.001). According to the research findings, it can be concluded that sensory-motor integration exercises can be used as an appropriate intervention in promoting and improving social skills and motor performance of children with autism spectrum. Results of this study can be helpful for therapists and educators who deal with autistic children.

Normative values of motor performance and their relationship with BMI status in Hong Kong preschoolers

This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3–5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P50 and P95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese.

Prediction of decline in activities of daily living using motor performance tests in older adults requiring long-term care

ObjectiveThis study aimed to predict decline in activities of daily living (ADL) in older adults requiring long-term care, using motor performance tests. MethodsThis prospective cohort study was conducted among 3948 older adults using day care services in Japan. ADL decline was assessed using the Functional Independence Measure at the start of day care service use and 12 months later. Grip strength (GS), one-leg standing (OLS), and comfortable walking speed (CWS) were measured as baseline motor performance tests. To predict ADL decline using motor performance tests, we calculated cut-off values using receiver operating characteristics curves and odds ratios using logistic regression analysis. ResultsIn total, 521 participants had ADL decline at 12 months of follow-up. The cut-off values for each motor performance test were as follows (for men/women): GS < 24 kg/16 kg, OLS < 2 s/3 s, and CWS < 0.77 m/s/0.71 m/s. The odds ratios based on the number of items with scores below the cut-off were 1.84 for one item, 3.19 for two items, and 5.20 for three items. ConclusionMotor performance tests are effective in predicting ADL decline in older adults requiring long-term care, and combining the results of multiple items is even more effective.

Selection-Dependent Differences in Youth Elite Basketball Players’ Relative Age, Maturation-Related Characteristics, and Motor Performance

ABSTRACT Purpose: The aim of the present study was to investigate the influence of players’ relative age, maturation-related characteristics, and motor performance tests on two different stages of talent selection (regional and national level) in youth elite basketball. Methods: Relative age, maturation-related variables (height, weight, maturity offset, maturity timing) and motor performance (Countermovement jump, Standing long jump, Modified agility T-test, Linear sprint 20 m) of N = 68 male youth basketball players (M age = 14.39 ± 0.28 years) were assessed during the initial selection tournament for the German U15 national team. Pre-selection biases regarding relative age and maturity timing on the regional level were investigated utilizing one-sample t-tests. Differences in relative age, maturation-related characteristics and motor performance between players selected (n = 27) and non-selected (n = 41) for the youth national team were examined via independent samples’ t-tests and logistic regression analyses. Results: Strong pre-selection biases toward early-born and early-maturing players were confirmed on the regional level. Significant advantages in height and weight and higher values in maturity offset and maturity timing were found for selected players. Among the motor variables, only Countermovement jump performance was significantly better in selected players. When controlling for relative age and biological maturation regression models including motor performance variables did not significantly discriminate players’ selection status. Conclusion: Coaches working in national, but also preceding selection stages (regional and club level) should raise their awareness to relative age and biological maturation when evaluating players’ potential and current (motor) performance.

Xingnaojing injection alleviates cerebral ischemia/reperfusion injury through regulating endoplasmic reticulum stress in Vivo and in Vitro

BackgroundXingnaojing (XNJ) injection, an extract derived from traditional Chinese medicine, is commonly used to treat ischemic stroke (IS). Previous studies have shown that XNJ has the ability to alleviate apoptosis in cerebral ischemia-reperfusion injury. However, the potential mechanisms have not been clarified. ObjectiveTo identify the neuroprotective effect of XNJ and explore whether XNJ inhibits cell apoptosis associated with endoplasmic reticulum stress (ERS) after IS. MethodsIn this study, cultured hippocampal neurons from mouse embryos and Sprague-Dawley rats were assigned randomly to four groups: sham, model, XNJ, and edaravone. The treatment groups were administered 2 h after modelling. Neurological deficit scores and motor performance tests were performed after 24 h of modelling. Additionally, pathomorphology, cell apoptosis and calcium content were evaluated. To ascertain the expression of ERS proteins, western blotting and polymerase chain reaction were employed. ResultsThe results indicated that XNJ treatment resulted in a notable decrease in infarct volume, apoptosis and missteps compared with the model group. XNJ also exhibited improvements in neurological function, grip strength and motor time. The calcium content significantly reduced in XNJ group. The XNJ administration resulted in a reduction in the levels of proteins associated with ERS including CHOP, GRP78, Bax, caspase-12, caspase-9, and cleaved-caspase-3, but an increase of the Bcl-2/Bax ratio. Furthermore, the downregulation of mRNA expression of CHOP, GRP78, caspase-12, caspase-9, and caspase-3 was confirmed in both cultured neurons and rat model. ConclusionThese findings suggest that XNJ may alleviate apoptosis by modulating the ERS-induced apoptosis pathway, making it a potential novel therapeutic approach for ischemic stroke.

Whole-brain mapping of increased manganese levels in welders and its association with exposure and motor function

Although manganese (Mn) is a trace metal essential for humans, chronic exposure to Mn can cause accumulation of this metal ion in the brain leading to an increased risk of neurological and neurobehavioral health effects. This is a concern for welders exposed to Mn through welding fumes. While brain Mn accumulation in occupational settings has mostly been reported in the basal ganglia, several imaging studies also revealed elevated Mn in other brain areas. Since Mn functions as a magnetic resonance imaging (MRI) T1 contrast agent, we developed a whole-brain MRI approach to map in vivo Mn deposition differences in the brains of non-exposed factory controls and exposed welders. This is a cross-sectional analysis of 23 non-exposed factory controls and 36 exposed full-time welders from the same truck manufacturer. We collected high-resolution 3D MRIs of brain anatomy and R1 relaxation maps to identify regional differences using voxel-based quantification (VBQ) and statistical parametric mapping. Furthermore, we investigated the associations between excess Mn deposition and neuropsychological and motor test performance. Our results indicate that: (1) Using whole-brain MRI relaxometry methods we can generate excess Mn deposition maps in vivo, (2) excess Mn accumulation due to occupational exposure occurs beyond the basal ganglia in cortical areas associated with motor and cognitive functions, (3) Mn likely diffuses along white matter tracts in the brain, and (4) Mn deposition in specific brain regions is associated with exposure (cerebellum and frontal cortex) and motor metrics (cerebellum and hippocampus).

ИССЛЕДОВАНИЯ РЕСУРСА ИЗОЛЯЦИИ ЛИНЕЙНОГО ЭЛЕКТРОДВИГАТЕЛЯ НА ПРИМЕРЕ ЗЕРНООЧИСТИТЕЛЬНОЙ МАШИНЫ

This article presents the results of operational tests of the linear electric motor performance. The study was conducted using grain cleaning machines as an example. The tests formed the basis for determining the effect of loads under various operating modes and of external factors on the insulation state of the linear motor windings. The tests established dependences of the insulation resistance of the electric motor windings on the operating time and environmental factors.

Baby Massage has an Impact on Weight and Motor Skill of Babies Aged 1 to 12 Months

Introduction: Underweight or overweight is a child health problem in Indonesia. This is the most important anthropometric measurement for seeing the physical development of newborns. Underweight or overweight which can cause motor delays is closely related to infant growth. Objective: to ascertain how baby massage affects the growth of baby weight and gross motor abilities. Method: Pre-experimental research using a pretest-posttest one-group design is the kind of study being conducted. Forty newborns were selected as a sample using basic random sampling. Infants were selected based on the inclusion criteria of age 1 – 12 months, did not experience chronic neuromuscular disorders, were still breastfeeding, were born through normal delivery, and came to the Berua Health Center, Makassar City from May to July 2024. Body weight was measured using a baby scale and gross motor skills were measured using the Infant Motor Performance Test. For each significant variable, parametric analysis was conducted with a paired t-test (p &lt;0.05). Results: The results showed Body weight increased significantly (p = 0.001) and gross motor data increased significantly (p = 0.014) in the results. Conclusion: massage can influence the development of body weight and gross motor skills in babies aged one to twelve months. The study found that providing infant massage for 10-15 minutes twice a week for one month can have an impact on weight gain and gross motor skills of infants aged 1-12 months. In addition, the data also revealed that providing infant massage has a significant impact on improving gross motor skills of infants aged 1-12 months

EXAMINING THE LINK BETWEEN MOTOR FITNESS AND MORPHOLOGY IN 10-YEAR-OLD CHILDREN

The objective of this study was to investigate the relationship between motor fitness and morphological factors, including anthropometric measurements and body composition, in a cohort of 10-year-old children. The sample consisted of 32 boys (mean age 10.24 ± 0.22 years, body height: 147.12 ± 6.11 cm, body mass: 42.14 ± 11.02 kg, body mass index: 19.41 ± 4.16 kg/m2) and 29 girls (mean age 10.12 ± 0.20 years, body height: 145.31 ± 7.68 cm, body mass: 40.10 ± 8.76 kg, body mass index: 18.91 ± 3.58 kg/m2). Anthropometric and body composition variables encompassed body height (BH), body mass (BM), body mass index (BMI), body fat mass (BFM), and free-fat mass (FFM). The motor fitness tests, designed to evaluate strength, coordination, speed and aerobic fitness, included standing long jump (SLJ), medicine ball throw (MBT), sit-ups in 30 seconds test (SUT), hand tapping test (HTT), obstacle course backwards test (OCB), and shuttle run test (SRT). While there were no notable differences between boys and girls in terms of morphology, for MBT (p = 0.011) and HTT (p = 0.016) fitness tests significant sex-differences were observed. Except HTT, all motor variables showed small to moderate correlations with morphological variables. Through the utilization of regression analysis, it was determined that BMI (r = 0.201 - 0.389) and BFM (r = 0.166 - 0.418) were the most influential predictor variables for the majority of motor variables. These findings suggest that anthropometry and body composition have a moderate impact on performance in motor tests that assess strength, body coordination, and aerobic fitness.

High-intensity interval training ameliorates spatial and recognition memory impairments, reduces hippocampal TNF-alpha levels, and amyloid-beta peptide load in male hypothyroid rats

Thyroid hormones are critical for healthy brain functions at every stage of life. Hypothyroidism can cause severe cognitive dysfunction in patients who do not receive adequate treatment. Although thyroid hormone replacement alleviates cognitive decline in hypothyroid patients, there are studies showing that there is no complete recovery. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) in hypothyroid rats on spatial and recognition memory, neuroinflammation, amyloid-beta load and compare these effects with T3 replacement. Hypothyroidism was induced and maintained by administration of 6-n-propyl-2-thiouracil (PTU) with their drinking water to 6-weeks-old male Sprague–Dawley rats for 7 weeks. The animals exercised in the treadmill according to the HIIT protocol for four weeks. T3 was injected intraperitoneally daily during the last two weeks of the study. All animals performed in the elevated plus maze test, Morris water maze test, novel object recognition test, and rotarod motor performance test in the last week of the study and then the animals were sacrificed. Amyloid beta (1−42) and TNFα levels were measured in the prefrontal cortex and hippocampus by ELISA. Anxiety-like behaviors did not significantly differ between groups. T3 replacement with or without HIIT increased motor performance in PTU-treated rats. HIIT and/or T3 replacement increased the exercise performance. HIIT and/or T3 replacement alleviated spatial and recognition memory impairments and normalized TNFα and amyloid-beta levels in the hippocampus in hypothyroid rats. In summary, regular physical exercise may have potential benefits in preserving cognitive functions in hypothyroid patients.

Bidirectional associations of high-level cognitive domains with hand motor function and gait speed in high-functioning older adults: A 7-year study

BackgroundWhether age-related decline in the musculoskeletal system may contribute to a decline in cognitive performance or vice versa is unclear. Understanding the direction of their associations and the extent to which upper and lower extremities similarly predict subtle changes in high-level cognitive performance will help elucidate their mechanisms, especially that of the hand dexterity. MethodsWe evaluated the bidirectional associations of motor performance and high-level cognitive domains in 165 highly cognitively and physically healthy older adults. Motor performance tests consisted of handgrip strength, hand dexterity, assessed with the Purdue Pegboard Test (PPT), and usual and maximum gait speeds. High-level cognitive measures included executive function and information processing speed. The Trail Making Test (TMT)B and the letter and category fluency tests (LFT and CFT) evaluated executive function, while the TMTA and Digit Symbol assessed processing speed. Measurements were taken at baseline and at 2-, 5- and 7-year follow-up. ResultsGeneralized linear mixed-effect models showed that baseline hand dexterity and its trajectory predicted changes in TMTB, CFT, TMTA, and Digit Symbol over time, and vice versa. Baseline maximum gait speed was associated with LFT over time and vice versa. No associations were found for handgrip and usual gait speed. ConclusionThe positive bidirectional association observed both in hand dexterity and maximum gait speed with executive function performance and that of hand dexterity with processing speed over time highlights a reciprocal relationship where each factor affects the other and both factors are dependent on each other, suggesting commonality in their neural basis.

Opportunities and Limits of a Disciplinary Repository Using the Example MO|RE data (eResearch Infrastructure for Motor Research Data)

Out of two funding periods by the German Research Foundation resulted the first disciplinary repository for sports science motor activity research data MO|RE data. MO|RE data addresses sports scientists, researchers from related disciplines and practitioners such as teachers and educators, which work with or generate human motor performance test data as well. It has five main functions: publishing, storing, searching, citing and mapping. There are still some limitations as well as not exploited opportunities. Opportunities include among others the international expansion. Limitations are e.g., that linking health and motor test data is difficult due to data protection law. The sharing of sensitive data is not possible with the current concept and needs further solutions as e.g., remote access or workstations for guest researchers. In future, those data sets must be kept in mind to cover the requirements of research data management in sports science. Overall, the need for further development and optimization of MO|RE data repository in sports science becomes apparent to maximize its potential and ensure that it meets the evolving needs of researchers in the field.

Customizable Open-Source Rotating Rod (Rotarod) Enables Robust Low-Cost Assessment of Motor Performance in Mice.

Reliable measurements of motor learning and coordination in mice are fundamental aspects of neuroscience research. Despite the advent of deep-learning approaches for motor assessment, performance testing on a rotating rod (rotarod) has remained a staple in the neuroscientist's toolbox. Surprisingly, commercially available rotarod instruments offer limited experimental flexibility at a relatively high cost. In order to address these concerns, we engineered a highly-customizable, low-budget rotarod device with increased functionality. Here, we present a detailed guide to assemble this rotarod using simple materials. Our apparatus incorporates a variation of interchangeable rod sizes and designs which provides for adjustable testing sensitivity. Moreover, our rotarod is driven by open-source software enabling bespoke acceleration ramps and sequences. Finally, we report the strengths and weaknesses of each rod design following multiday testing on cohorts of C57BL/6 mice. We expect explorations in deviant rod types to provide a foundation for the development of increasingly sensitive models for motor performance testing along with low-budget alternatives for the research community.

AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C

Type 4C Charcot-Marie-Tooth (CMT4C) demyelinating neuropathy is caused by autosomal recessive SH3TC2 gene mutations. SH3TC2 is highly expressed in myelinating Schwann cells. CMT4C is a childhood-onset progressive disease without effective treatment. Here, we generated a gene therapy for CMT4C mediated by an adeno-associated viral 9 vector (AAV9) to deliver the human SH3TC2 gene in the Sh3tc2-/- mouse model of CMT4C. We used a minimal fragment of the myelin protein zero (Mpz) promoter (miniMpz), which was cloned and validated to achieve Schwann cell-targeted expression of SH3TC2. Following the demonstration of AAV9-miniMpz.SH3TC2mycvector efficacy to re-establish SH3TC2 expression in the peripheral nervous system, we performed an early as well as a delayed treatment trial in Sh3tc2-/- mice. We demonstrate both after early as well as following late treatment improvements in multiple motor performance tests and nerve conduction velocities. Moreover, treatment led to normalization of the organization of the nodes of Ranvier,which is typically deficient in CMT4C patients and Sh3tc2-/- mice, along with reduced ratios of demyelinated fibers, increased myelin thickness and reduced g-ratios at both time points of intervention. Taken together, our results provide a proof of concept for an effective and potentially translatable gene replacement therapy for CMT4C treatment.