Improve Muscle Function Research Articles

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery: A systematic review.

Lack of mobilization and prolonged stay in the intensive care unit (ICU) are major factors resulting in the development of ICU-acquired muscle weakness (ICUAW). ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery, and may be a risk factor for prolonged duration of mechanical ventilation, associated with a higher risk of readmission and higher mortality. Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay. Neuromuscular electrical stimulation (NMES) is an alternative modality of exercise in patients with muscle weakness. A major advantage of NMES is that it can be applied even in sedated patients in the ICU, a fact that might enhance early mobilization in these patients. To evaluate safety, feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery. We performed a search on Pubmed, Physiotherapy Evidence Database (PEDro), Embase and CINAHL databases, selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials (RCTs) that included implementation of NMES in patients before after cardiac surgery. RCTs were assessed for methodological rigor and risk of bias via the PEDro. The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function. Ten studies were included in our systematic review, resulting in 703 participants. Almost half of them performed NMES and the other half were included in the control group, treated with usual care. Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery. Functional capacity was assessed in 8 studies via 6MWT or other indices, and improved only in 1 study before and in 1 after cardiac surgery. Nine studies explored the effects of NMES on muscle strength and function and, most of them, found increase of muscle strength and improvement in muscle function after NMES. NMES was safe in all studies without any significant complication. NMES is safe, feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery, but has no significant effect on functional capacity.

Unveiling the Potential of Nelumbo nucifera-Derived Liensinine to Target The Myostatin Protein and to Counteract Muscle Atrophy.

Muscle atrophy refers to a decline in muscle mass and function, which has become a global concern due to the aging population. Various clinical trials have investigated the inhibitors of myostatin (MSTN). They have shown promising improvements in muscle function and quality of life. However, there are no drugs specifically targeting MSTN that have been approved for clinical use. In this study, we virtually screened liensinine (LIE), a food (Nelumbo nucifera)-derived compound, with low toxicity, from over 1.1 million compounds. We subsequently identified it as a potential candidate that targets MSTN by a cellular thermal shift assay (CETSA) and drug affinity response target stability (DARTS) assay. Further validation through cellular and in vivo studies demonstrated its promising potential in combating muscle atrophy. The mechanism of action may involve hindering the interaction between MSTN and the activin receptor type IIB (ActRIIB) and downregulating the expression of downstream proteins, including the muscle RING-finger protein-1 (MuRF-1) and muscle atrophy F-box (MAFbx)/Atrogin-1, ultimately promoting muscle regeneration. These results provide a strong foundation for future studies to explore the therapeutic potential of LIE in clinical settings.

Photobiomodulation therapy (red/NIR LEDs) reduced the length of stay in intensive care unit and improved muscle function: A randomized, triple-blind, and sham-controlled trial.

Photobiomodulation therapy (PBMT) has been widely used to improve strength, fatigue resistance and increase muscle mass in healthy individuals. These effects could help critically ill patients admitted to intensive care units (ICUs) who show reduced mobility and muscle strength. ICU-acquired weakness lessens overall health and increases the patient's length of stay in the ICU. This study evaluated the effects of PBMT using low intensity light-emitting diodes (LEDs) on the mobility and muscle strength (functional capacity) and length of stay of patients admitted to hospital ICU. This randomized, triple-blind, sham-controlled trial was conducted in a hospital ICU. Sixty patients were randomly assigned to two equal groups: (a) PBMT and (b) Sham. PBMT was applied daily to patients until their discharge from the ICU, using a flexible neoprene array of 264 LEDs (120 at 635 nm, 1.2 mW each; 144 at 880 nm, 15 mW each) for 90s (207.36 Joules) at each site. Ten sites were located bilaterally on the thighs, legs, arms, and forearms ventrally and dorsally, 15 min totaling 2,073.6Joules per session. Outcomes were length of stay (in h) until discharge from the ICU, muscle strength by the Medical Research Council (MRC) score and handgrip dynamometry (HGD), patient mobility by Intensive Care Unit Mobility Scale (IMS) and the Simplified Acute Physiology Score 3 (SAPS 3) for predicting mortality of patients admitted to the ICU. PBMT reduced the average length of stay in the ICU by ~30% (p = 0.028); increased mobility (IMS: 255% vs. 110% p = 0.007), increased muscle strength (MRC: 12% vs. -9% p = 0.001) and HGD (34% vs. -13% p < 0.001), and the SAPS3 score was similar (p > 0.05). The results suggest that daily PBMT can reduce the length of stay of ICU patients and increase muscle strength and mobility.

1867 Efficacy and safety of metformin as a therapy for older people with sarcopenia and frailty - the MET-PREVENT randomised trial

Abstract Introduction Metformin has pleiotropic biological effects which might improve muscle function in older people. The MET-PREVENT trial tested the efficacy and safety of metformin as a therapy for sarcopenia and frailty in older people. Methods Double blind, randomised, parallel-group, placebo-controlled trial. Participants aged ≥65 with walk speed &amp;lt;0.8m/s and low muscle strength (handgrip &amp;lt;16kg for women, &amp;lt;27kg for men, or 5x sit to stand &amp;gt;15s) were recruited from primary care and hospital clinics. Participants were randomised 1:1 using a web-based interactive system to receive 4 months of 500mg metformin or matching placebo 3x/day. The primary outcome, analysed by intention to treat, was the between-group difference in 4m walk speed at 4 months, adjusted for baseline values. Secondary outcomes included grip strength, short physical performance battery, six-minute walk distance, muscle mass by bioimpedance, quality of life and activities of daily living. All adverse events were recorded. Results Seventy-two participants were randomised, mean age 80 (SD 6) years. 42 (58%) were women, 42 (58%) were frail (Fried score ≥3); mean baseline 4m walk speed was 0.59 m/s (SD 0.22). 70 (97%) completed the trial (metformin 34/36, placebo 36/36). 14 (40%) discontinued metformin and 5 (14%) discontinued placebo. There was no difference in the primary outcome between the metformin (0.57 m/s [SD 0.19] m/s) and placebo group (0.58 m/s [SD 0.24]); adjusted treatment effect was 0.001 m/s (95%CI -0.06, 0.06); p=0.96. There was no significant effect on measures of muscle mass, physical performance, quality of life or activities of daily living. The metformin group had more adverse events (110 vs 77) and more hospital admissions (12 vs 3) Conclusions MET-PREVENT achieved successful recruitment with high retention rates, however metformin did not improve physical performance and was poorly tolerated with high rates of adverse events in older people with sarcopenia.

Dietary oleic acid intake increases the proportion of type 1 and 2X muscle fibers in mice

Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear. This study aimed to determine the effect of oleic acid on the muscle fiber types and endurance capacity. An in vivo mouse model was used, and mice were fed a 10% oleic acid diet for 4 weeks. Two different skeletal muscles, slow soleus muscle with the predominance of slow-twitch fibers and fast extensor digitorum longus (EDL) muscle with the predominance of fast-twitch fibers, were used. We found that dietary oleic acid intake improved running endurance and altered fiber type composition of muscles, the proportion of type 1 and 2X fibers increased in the soleus muscle and type 2X increased in the EDL muscle. The fiber type shift in the EDL muscle was accompanied by an increased muscle TAG content. In addition, blood triacylglycerol (TAG) and non-esterified fatty acid levels decreased during exercise. These changes suggested that lipid utilization as an energy substrate was enhanced by oleic acid. Increased proliferator-activated receptor γ coactivator-1β protein levels were observed in the EDL muscle, which potentially enhanced the fiber type transitions towards type 2X and muscle TAG content. In conclusion, dietary oleic acid intake improved running endurance with the changes of muscle fiber type shares in mice. This study elucidated a novel functionality of oleic acid in skeletal muscle fiber types. Further studies are required to elucidate the underlying mechanisms. Our findings have the potential to contribute to the field of health and sports science through nutritional approaches, such as the development of supplements aimed at improving muscle function.

K-taping (coloured sticking adhesive bands): myth or reality?

The use of Kinesiotaping (KT) has become common in the treatment and prevention of musculoskeletal injuries. This article covers the ten main myths encountered on a daily basis, examining the evidence from recent data (systematic reviews and meta-analyses). With current available data, there is a relative evidence regarding some effect upon short-term pain relief, improved mobility, better joint stability, drainage of edema, and improve muscle function. Concerning the prevention of musculoskeletal injuries, it seems that the effectiveness of KT is still questionable. Overall, there are few publications with a high-level of evidence that can support all myths surrounding K-taping.

The Effectiveness of Blood Flow Restriction Technique Combined with Low-Resistance Exercise in the Postoperative Rehabilitation of Patients Following Knee Surgery: A Narrative Review and Update of Evidence-Based Physiotherapy Practice

&lt;b&gt;Background:&lt;/b&gt; Blood flow restriction (BFR) therapy has emerged as a promising rehabilitation approach after knee surgery. The technique involves the use of a tourniquet or cuff to limit blood flow to the affected limb during low-resistance exercise, which creates a hypoxic environment thought to stimulate muscle growth and improve muscle function. &lt;b&gt;Objective:&lt;/b&gt; Our scoping review aims to examine the current literature on the effectiveness of BFR combined with low-resistance exercise on rehabilitation after knee surgery. &lt;b&gt;Method: &lt;/b&gt;The Google Scholar, PubMed, and PEDro databases were searched using relevant key-words. Studies that met the inclusion criteria were selected for analysis. The data from the selected studies were analyzed, categorized, and summarized to provide an overview of the findings. &lt;b&gt;Results:&lt;/b&gt; In total, 12 studies met the inclusion criteria and were included in the review. Outcomes such as pain, strength, and range of motion were assessed. &lt;b&gt;Conclusion: &lt;/b&gt;The results suggest that BFR and low-resistance exercise can be effective in improving patient outcomes following knee surgery. However, the heterogeneity of the studies made it difficult to determine the most effective approach. Further research is needed to identify the optimal dosage, frequency, and duration of BFR and low-resistance exercise for knee surgery rehabilitation.

Omega-3 polyunsatured fatty acids and physical performance across the lifespan: a narrative review.

Physical performance is a major contributor of mobility and independence during older life. Despite a progressive decline in musculoskeletal function starts from middle age, several factors acting during the life-course can negatively influence musculoskeletal functional capacities. Lifestyle interventions incorporating nutrition and physical exercise can help maximizing the muscle functional capacities in early life as well as preserving them later in life. Among various dietary compounds, omega-3 polyunsaturated fatty acids (PUFAs) are gaining growing attention for their potential effects on muscle membrane composition and muscle function. Indeed, several pathways are enhanced, such as an attenuation of pro-inflammatory oxidative stress, mitochondrial function, activation of the mammalian target of rapamycin (mTOR) signaling and reduction of insulin resistance. We performed a narrative review to explore the existing literature on the relationship between omega-3 PUFAs and physical performance across the life-course. Growing evidence from randomized controlled trials (RCTs) suggests beneficial effects of omega-3 PUFAs on muscle function, including physical performance parameters in mid to later life. On the other hand, despite a direct association in early life is not available in literature, some mechanisms by which omega-3 PUFAs may contribute to improved adult physical performance could be hypothesized. Omega-3 PUFAs are gaining growing attention for their positive effect on muscle function parameters. The integration of physical function measures in future studies would be of great interest to explore whether omega-3 PUFAs could contribute to improved muscle function, starting from early life and extending throughout the lifespan. However, larger and high-quality RCTs are needed to fully elucidate the beneficial effects of omega-3 PUFAs supplementation on muscle mass and function.

Nutritional Intervention Improves Muscle Mass and Physical Performance in the Elderly in the Community: A Systematic Review and Meta-Analysis.

Nutritional supplements have been extensively used as health interventions for the elderly. However, with the spread of COVID-19, no consensus exists on whether nutritional interventions could improve muscle mass and physical activity in community-dwelling older adults. To conduct a systematic review and meta-analysis to explore the effects of different nutritional interventions on muscle mass and physical performance in the elderly, we searched PubMed, Web of Science, Elsevier, and Cochrane databases from their founding dates to December 2023. The meta-analysis was performed using RevMan5.3 software. Only randomized controlled trials (RCTs) were considered, and the overall mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. There were 33 studies comprising 3579 elderly persons meeting the inclusion criteria. Comprehensive analysis suggested that the intervention effect of fat-free mass (FFM), appendix skeletal muscle mass (ASMM), handgrip strength (HGS), gait speed, and short physical performance battery (SPPB) score was higher in the nutritional supplement group than in the control group. The results of subgroup analysis demonstrated that protein supplementation (SMD = 0.82, p < 0.0001) had an optimal effect on ASMM (SMD = 0.89, p < 0.0001) and FFM (MD = 2.09, p < 0.0001) in the elderly. Vitamin D supplementation (SMD = 0.52, p < 0.0001) had a marginal effect on ASMM, and energy supplementation (SMD = 0.39, p = 0.0005) had the lowest effect. Moreover, nutritional interventions had the most significant impact on HGS (MD = 1.06, p < 0.0001) and TUG (MD = 0.14, p < 0.0001) in individuals aged 65-75 years old, with positive effects on FFM (MD = 1.62, p < 0.0001) and HGS (MD = 0.82, p < 0.0001) when compared to healthy elderly individuals, and had greater effect on ASMM (SMD = 0.69, p < 0.0001) than on the elderly with sarcopenia. Nutritional supplements can enhance muscle mass and physical performance in the elderly, while protein is recommended for muscle function. The golden period for implementing nutritional interventions to improve muscle function is before the age of 75 years. However, the impact of nutritional interventions varies with age and population. Given the limited evidence on nutritional interventions, more detailed and high-quality studies are highly warranted in the future.

The potential role of creatine supplementation in neurodegenerative diseases.

The maintenance of energy balance in the body, especially in energy-demanding tissues like the muscles and the central nervous system, depends on creatine (Cr). In addition to improving muscle function, Cr is necessary for the bioenergetics of the central nervous system because it replenishes adenosine triphosphate without needing oxygen. Furthermore, Cr possesses anti-oxidant, anti-apoptotic, and anti-excitotoxic properties. Clinical research on neurodegenerative illnesses has shown that Cr supplementation results in less effective outcomes. With a brief update on the possible role of Cr in human, animal, and in vitro experiments, this review seeks to offer insights into the ideal dosage regimen. Using specified search phrases, such as "creatine and neurological disorder," "creatine supplementation and neurodegenerative disorders," and "creatine and brain," we searched articles in the PubMed database and Google Scholar. We investigated the association between creatine supplementation and neurodegenerative illnesses by examining references. The neuroprotective effects of Cr were observed in in vitro and animal models of certain neurodegenerative diseases, while clinical trials failed to reproduce favorable outcomes. Determining the optimal creatinine regime for increasing brain creatinine levels is essential for maintaining brain health and treating neurodegeneration.

BIO101 stimulates myoblast differentiation and improves muscle function in adult and old mice.

Muscle aging is associated with a consistent decrease in the ability of muscle tissue to regenerate following intrinsic muscle degradation, injury or overuse. Age-related imbalance of protein synthesis and degradation, mainly regulated by AKT/mTOR pathway, leads to progressive loss of muscle mass. Maintenance of anabolic and regenerative capacities of skeletal muscles may be regarded as a therapeutic option for sarcopenia and other muscle wasting diseases. Our previous studies have demonstrated that BIO101, a pharmaceutical grade 20-hydroxyecdysone, increases protein synthesis through the activation of MAS receptor involved in the protective arm of renin-angiotensin-aldosterone system. The purpose of the present study was to assess the anabolic and pro-differentiating properties of BIO101 on C2C12 muscle cells in vitro and to investigate its effects on adult and old mice models in vivo. The effects of BIO101 on C2C12 differentiation were assessed using myogenic transcription factors and protein expression of major kinases of AKT/mTOR pathway by Western blot. The in vivo effects of BIO101 have been investigated in BIO101 orally-treated (50mg/kg/day) adult mice (3months) for 28days. To demonstrate potential beneficial effect of BIO101 treatment in a sarcopenic mouse model, we use orally treated 22-month-old C57Bl6/J mice, for 14weeks with vehicle or BIO101. Mice body and muscle weight were recorded. Physical performances were assessed using running capacity and muscle contractility tests. Anabolic properties of BIO101 were confirmed by the rapid activation of AKT/mTOR, leading to an increase of C2C12 myotubes diameters (+26%, P<0.001). Pro-differentiating effects of BIO101 on C2C12 myoblasts were revealed by increased expression of muscle-specific differentiation transcription factors (MyoD, myogenin), resulting in increased fusion index and number of nuclei per myotube (+39% and +53%, respectively, at day 6). These effects of BIO101 were like those of angiotensin (1-7) and were abolished with the use of A779, a MAS receptor specific antagonist. Chronic BIO101 oral treatment induced AKT/mTOR activation and anabolic effects accompanied with improved physical performances in adult and old animals (maximal running distance and maximal running velocity). Our data suggest beneficial anabolic and pro-differentiating effects of BIO101 rendering BIO101 a potent drug candidate for treating sarcopenia and possibly other muscle wasting disorders.

2023 아시아 청소년 우슈 선수권대회 제3국제경기투로의 경기력 향상 방안 연구

This study analyzed the competition content of 14 sports by 5 youth representative athletes who participated in Group A of the 11th asian junior wushu championships in 2023 and reached the following conclusions. First, the vertical velocity must be increased by the reaction force of the ground to increase the height of the jump, and it has been shown that a safe landing can be achieved only by performing a kick with a leisurely staying in the air. Second, it was found that the Bow Stance should keeping the femur of the front leg horizontal, the Butterfly Stance should keeping the calf of the back leg and the inner side of the foot close to the floor, and for the Front and Back Sweep, the rotation is efficient when it is controlled to prevent the center of gravity from swinging around the rotation axis. Third, it has been revealed that improving muscle function control through repetitive training for shaking of movements. Fourth, it has been found that high scores are obtained for the level of acting only when the movement standard and moderation are clear and so the coordination of movements and the harmony of weapons are well organized.

Comparative effects of Bowen therapy and tennis ball technique on pain and functional disability in patients with thoracic myofascial pain syndrome

BackgroundThoracic myofascial pain syndrome is a clinical problem arising from the muscles and soft tissues of thoracic region, which include the mid and upper back area. Risk factors associated with myofascial pain syndrome are muscle overuse and repetitive strain, poor posture, trauma or injury, emotional and psychological stresses. The management of myofascial pain syndrome (MPS) typically involves a multidimensional approach that focuses on relieving pain, reducing muscle tension, and improving muscle function. Bowen therapy and tennis ball technique are also recommended for treating myofascial pain syndrome.ObjectiveThe objective of this study was to compare the effects of Bowen therapy and tennis ball technique on pain and functional disability in patients with thoracic myofascial pain syndrome.MethodsIt was a randomized clinical trial conducted on thirty patients. It was carried out in physiotherapy outpatient department of D.H.Q Hospital, Kasur. Non-probability convenience sampling technique was used. Data collection was done from the patients of thoracic myofascial pain syndrome by using Numeric Pain Rating Scale (NPRS) for pain and Pain Disability Questionnaire (PDQ) for functional disability. Participants were randomly allocated into two groups using computer generated random number method. Group A received Bowen therapy, and group B received tennis ball technique. Outcome measures were measured at baseline, after second week treatment session and after fourth week with three sessions in a week on alternate days. Data analysis was done by using Statistical Package for the Social Sciences (SPSS) version 26.ResultsThere was significant difference between the mean values of NPRS and PDQ in both groups at baseline, second week and fourth week with p value < 0.05. The results indicated that both treatments were significant but Bowen therapy is more effective treatment than tennis ball technique. Within-group difference calculated with repeated-measure ANOVA indicated that there was significant difference from pre- to post-values of both groups.ConclusionThis study concluded that Bowen therapy produced statistically significant and clinically relavant results for all the outcome measures. Trial registration. (IRCT20190717044238N7).

Gait training using a wearable robotic hip device for incomplete spinal cord injury: A preliminary study

Context/Objective To explore changes in gait functions for patients with chronic spinal cord injury (SCI) before and after standard rehabilitation and rehabilitation with a wearable hip device, explore the utility of robot-assisted gait training (RAGT), and evaluate the safety and dose of RAGT. Design Single-arm, open-label, observational study. Setting A rehabilitation hospital. Participants Twelve patients with SCI. Interventions Standard rehabilitation after admission in the first phase. RAGT for two weeks in the second phase. Outcome measures Self-selected walking speed (SWS), step length, cadence, and the 6-minute walking distance were the primary outcomes. Walking Index for SCI score, lower extremity motor score, and spasticity were measured. Walking abilities were compared between the two periods using a generalized linear mixed model (GLMM). Correlations between assessments and changes in walking abilities during each period were analyzed. Results After standard rehabilitation for 66.1 ± 36.9 days, a period of 17.6 ± 3.3 days of RAGT was safely performed. SWS increased during both periods. GLMM showed that the increase in cadence was influenced by standard rehabilitation, whereas the limited step length increase was influenced by RAGT. During RAGT, the increase in step length was related to an increase in hip flexor function. Conclusions Gait speed in patients with SCI increased after rehabilitation, including RAGT, in the short-term. This increase was associated with improved muscle function in hip flexion at the start of RAGT. Trial Registration: This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR; UMIN000042025)

Twice-Weekly Outpatient Rehabilitation Intervention for Young Children With Spinal Muscular Atrophy Treated With Genetic-Based Therapies: Protocol for a Feasibility Study

Background Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder that causes muscle weakness and is the leading genetic cause of infant mortality worldwide. While no definitive cure exists, the approval of 3 genetic-based therapies in Canada since 2018 has led to significant improvements in muscle function for children with SMA. With that, there are no evidence-based rehabilitation interventions and minimal evidence on the combined effects of genetic-based therapies and rehabilitation. Objective This protocol describes the methodology to assess the feasibility of a twice-weekly outpatient rehabilitation intervention focusing on gross and fine motor function to inform the methodology and sample size of a definitive clinical trial. Methods We will conduct a single-center nonrandomized pilot and feasibility trial to explore an outpatient rehabilitation intervention for children aged 6 months to 3 years with SMA treated with genetic-based therapies. Participation in the study will occur over a 25-week period, with a baseline assessment visit followed by a 12-week intervention period and a 12-week nonintervention period. The rehabilitation intervention comprises weekly physical and occupational therapy for 11 weeks. Assessments will occur at baseline (week 0), end of intervention or early withdrawal (week 12), and follow-up (week 24). Predetermined feasibility indicators will evaluate study feasibility across process (recruitment rates, eligibility criteria, adherence rates, retention rates, questionnaire suitability, and acceptability), resource (time, implementation, and execution), management (materials and data), and scientific (safety, tolerability, and preliminary efficacy) domains. Results This project was funded in March 2022, and data will be collected between March 2023 and December 2023. Data analysis will occur between January 2024 and March 2024, with publication expected in the fall of 2024. The protocol for the feasibility trial will be considered successful if it meets the success criteria set out for the feasibility indicators. Indicators of specific interest include all process indicators, as well as time. Exploratory indicators will be reported. Pragmatically, the results of the feasibility trial will inform changes to the protocol and the start-up of a definitive multisite trial. Conclusions This novel twice-weekly outpatient rehabilitation intervention will be the first step toward filling the need for an evidence-based rehabilitation intervention for children with SMA treated with genetic-based therapies. It is expected that consistent and intensive rehabilitation therapy will augment functional gains being observed in this population. In the future, a definitive trial will measure the efficacy of the intervention. Trial Registration ClinicalTrials.gov NCT05638750; https://clinicaltrials.gov/study/NCT05638750 International Registered Report Identifier (IRRID) DERR1-10.2196/46363

Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH.

In clinical trials, burosumab ameliorates symptoms of pain, fatigue, and stiffness and improves performance on certain muscle function studies in patients with X-linked hypophosphatemia (XLH). This work aimed to determine if burosumab increases adenosine triphosphate (ATP) synthesis in skeletal muscle of treatment-naive adults with XLH, and if so, whether that correlates with improved muscle function. Ten untreated, symptomatic adults with XLH had ATP synthesis rates measured in the right calf using the 31P magnetic resonance spectroscopy saturation transfer technique. Baseline muscle function tests and symptoms of pain, fatigue, stiffness, and lower-extremity joint pain were quantified. All participants were treated with burosumab, 1 mg/kg every 4 weeks for 12 weeks. ATP synthesis rates and muscle function tests were repeated 2 weeks ("peak") and 4 weeks ("trough") after the third dose of burosumab. All symptoms improved with treatment. Performance on the 6-Minute Walk Test (6MWT) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates did not change over the 3 months of the study. When individuals whose performances on the 6MWT and STS test were at or better than the median outcome for those tests were compared to those whose outcomes were below the median, no difference was observed in the rate of change in ATP synthesis. Intracellular muscle concentrations of phosphate were normal. The improvement in the 6MWT and STS test without changes in muscle strength or ATP synthesis rates suggests that reductions in pain, fatigue, and stiffness may partly explain the improved performance. Intracellular phosphate in skeletal muscle is insulated from hypophosphatemia in XLH.

Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics.

Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, and subsequent paralysis are among the main features of this disease, which is defined as a neuromuscular disorder. ALS is a persistently progressive disease, and as motor neurons continue to degenerate, individuals with ALS experience a gradual decline in their ability to perform daily activities. Ultimately, muscle function loss may result in paralysis, presenting significant challenges in mobility, communication, and self-care. While the majority of ALS research has traditionally focused on pathogenic pathways in the central nervous system, there has been a great interest in muscle research. These studies were carried out on patients and animal models in order to better understand the molecular mechanisms involved and to develop therapies aimed at improving muscle function. This review summarizes the features of ALS and discusses the role of muscle, as well as examines recent studies in the development of treatments.

Supplementation for sarcopenia in chronic kidney disease updated literature review

Sarcopenia is the loss of muscle mass and strength, common in elderly patients and worsened by the presence of chronic kidney disease (CKD), which has a progressive decrease in the number of nephrons. Anaerobic physical exercise and protein supplementation are important for maintaining strength and muscle mass. Dietary interventions, such as greater protein intake, are essential to preserve and increase muscle mass. Leucine appears to be the most powerful amino acid in stimulating muscle anabolism. Testosterone and L-carnitine supplementation may also be helpful, but there is controversy regarding their use. Omega 3, vitamin D and calcium are supplements that can increase muscle mass and improve muscle function in patients with sarcopenia associated with CKD, but their dosages are still debatable. This review article aims to describe oral supplementation for sarcopenia and the kidney changes that they may cause. In summary, physical activity and protein supplementation are fundamental in the treatment of sarcopenia in patients with CKD.

Naringenin improves muscle endurance via activation of the Sp1-ERRγ transcriptional axis

Skeletal muscle function declines in the aging process or disease; however, until now, skeletal muscle has remained one of the organs most undertreated with medication. In this study, naringenin (NAR) was found to build muscle endurance in wild-type mice of different ages by increasing oxidative myofiber numbers and aerobic metabolism, and it ameliorates muscle dysfunction in mdx mice. The transcription factor Sp1 was identified as a direct target of NAR and was shown to mediate the function of NAR on muscle. Moreover, the binding site of NAR on Sp1 was further validated as GLN-110. NAR enhances the binding of Sp1 to the CCCTGCCCTC sequence of the Esrrg promoter by promoting Sp1 phosphorylation, thus upregulating Esrrg expression. The identification of the Sp1-ERRγ transcriptional axis is of great significance in basic muscle research, and this function of NAR has potential implications for the improvement of muscle function and the prevention of muscle atrophy.

Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study.

Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration. The safety and efficacy of efgartigimod were evaluated in the ADAPT study. Key efficacy outcome measures included Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Efgartigimod demonstrated significant improvement in both the MG-ADL and QMG scores. This post hoc analysis aimed to determine whether all subdomains of MG-ADL and QMG improved with efgartigimod treatment. Individual items of MG-ADL and QMG were grouped into four subdomains: bulbar, ocular, limb/gross motor and respiratory. Change from baseline over 10 weeks in each subdomain was calculated for each group. Greater improvements from baseline were seen across MG-ADL subdomains in participants treated with efgartigimod compared with placebo. These improvements were typically observed 1 to 2 weeks after the first infusion and correlated with reductions in IgG. Similar results were observed across most QMG subdomains. These post hoc analyses of MG-ADL and QMG subdomain data from ADAPT suggest that efgartigimod is beneficial in improving muscle function and strength across all muscle groups, leading to the observed efficacy in participants with gMG.