Chemistry, structure and function of approved oligonucleotide therapeutics.

Eighteen nucleic acid therapeutics have been approved for treatment of various diseases in the last 25 years. Their modes of action include antisense oligonucleotides (ASOs), splice-switching oligonucleotides (SSOs), RNA interference (RNAi) and an RNA aptamer against a protein. Among the diseases targeted by this new class of drugs are homozygous familial hypercholesterolemia, spinal muscular atrophy, Duchenne muscular dystrophy, hereditary transthyretin-mediated amyloidosis, familial chylomicronemia syndrome, acute hepatic porphyria, and primary hyperoxaluria. Chemical modification of DNA and RNA was central to making drugs out of oligonucleotides. Oligonucleotide therapeutics brought to market thus far contain just a handful of first- and second-generation modifications, among them 2'-fluoro-RNA, 2'-O-methyl RNA and the phosphorothioates that were introduced over 50 years ago. Two other privileged chemistries are 2'-O-(2-methoxyethyl)-RNA (MOE) and the phosphorodiamidate morpholinos (PMO). Given their importance in imparting oligonucleotides with high target affinity, metabolic stability and favorable pharmacokinetic and -dynamic properties, this article provides a review of these chemistries and their use in nucleic acid therapeutics. Breakthroughs in lipid formulation and GalNAc conjugation of modified oligonucleotides have paved the way to efficient delivery and robust, long-lasting silencing of genes. This review provides an account of the state-of-the-art of targeted oligo delivery to hepatocytes.

Effects of the COVID-19 Pandemic on Access to Education and Social Participation in Children and Adolescents with Duchenne Muscular Dystrophy in Switzerland.

Two-thirds of patients with Duchenne muscular dystrophy (DMD) have cognitive and neuropsychiatric problems. Concerning their quality of life, negative factors are the lack of qualifying education and social participation in sporting and leisure activities. Adapted assistance in education and participation in social life are thus important. During the coronavirus disease 2019 (COVID-19) pandemic, the pediatric population was less severely impacted by the disease, but by the restrictions associated. The aim of this study was to evaluate the impact of the COVID-19 pandemic regarding access to education and social participation for young patients with DMD in Switzerland. We conducted a survey study from May to August 2021 assessing the impact of the COVID-19 pandemic on access to education and social participation in 8 to 18 years old patients with DMD in Switzerland. Of 60 sent surveys, 40 were returned and included. Mean age of participants was 13.5 years (±3.1 standard deviation); 23/40 of the participants were wheelchair bound, 21/40 attended a special school, and 19/40 a regular school. Of the 22/40 participants receiving assistance at school, 7/40 reported a change caused by the pandemic: for 5/7, the assistance was paused. Of the 12 boys and adolescents attending sporting activities, 10 had to suspend these. Nine attended other leisure activities; for 3/9, these activities were paused. The COVID-19 pandemic had direct effects on school assistance, sporting, and leisure activities in young patients with DMD in Switzerland. It is important to ensure that school assistance and leisure activities are rapidly resumed.

COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients.

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1ß, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.

Transcript-Targeted Therapy Based on RNA Interference and Antisense Oligonucleotides: Current Applications and Novel Molecular Targets.

The development of novel target therapies based on the use of RNA interference (RNAi) and antisense oligonucleotides (ASOs) is growing in an exponential way, challenging the chance for the treatment of the genetic diseases and cancer by hitting selectively targeted RNA in a sequence-dependent manner. Multiple opportunities are taking shape, able to remove defective protein by silencing RNA (e.g., Inclisiran targets mRNA of protein PCSK9, permitting a longer half-life of LDL receptors in heterozygous familial hypercholesteremia), by arresting mRNA translation (i.e., Fomivirsen that binds to UL123-RNA and blocks the translation into IE2 protein in CMV-retinitis), or by reactivating modified functional protein (e.g., Eteplirsen able to restore a functional shorter dystrophin by skipping the exon 51 in Duchenne muscular dystrophy) or a not very functional protein. In this last case, the use of ASOs permits modifying the expression of specific proteins by modulating splicing of specific pre-RNAs (e.g., Nusinersen acts on the splicing of exon 7 in SMN2 mRNA normally not expressed; it is used for spinal muscular atrophy) or by downregulation of transcript levels (e.g., Inotersen acts on the transthryretin mRNA to reduce its expression; it is prescribed for the treatment of hereditary transthyretin amyloidosis) in order to restore the biochemical/physiological condition and ameliorate quality of life. In the era of precision medicine, recently, an experimental splice-modulating antisense oligonucleotide, Milasen, was designed and used to treat an 8-year-old girl affected by a rare, fatal, progressive form of neurodegenerative disease leading to death during adolescence. In this review, we summarize the main transcriptional therapeutic drugs approved to date for the treatment of genetic diseases by principal regulatory government agencies and recent clinical trials aimed at the treatment of cancer. Their mechanism of action, chemical structure, administration, and biomedical performance are predominantly discussed.

What Is in the Myopathy Literature?

ABSTRACT: We cover intensive care unit-acquired neuromuscular disorders associated with coronavirus disease 2019. Outcomes may be worse than expected in these patients, and there is some evidence that coronavirus disease 2019 causes myopathy directly. Corticosteroid regimens in Duchenne muscular dystrophy are addressed including outcomes in pulmonary and cardiac function. A recent article notes a continued diagnostic delay in Duchenne muscular dystrophy. An interesting report of a Canary Islands cohort of patients with oculopharyngeal muscular dystrophy is discussed. Features and clinical pearls related to a series of patients with limb-girdle muscle dystrophy R12 (anoctaminopathy) and a misdiagnosis of idiopathic inflammatory myopathy are provided. The last section on autoimmune myopathy includes articles on clinical and pathologic features associated with myositis-specific antibodies and dermatomyositis, the epidemiology of immune-mediated necrotizing myopathies (IMNMs) in Olmsted County, Minnesota, and features of a German cohort of hydroxy-3-methylglutaryl coenzyme A reductase-associated IMNM. A recent article proposes the benefit of early intravenous immunoglobulin use for adults with IMNM. We also highlight a report of 2 unusual cases of antisignal recognition particle myopathy presenting with asymmetric distal weakness.

Impact of the COVID-19 pandemic on neuromuscular rehabilitation setting. Part 2: patients and families' views on the received health care during the pandemic.

This study explored views of users with muscular dystrophies and their caregivers on staff-user relationships and the treatments provided by a Rehabilitation Centre during the pandemic. Patients and relatives were asked to anonymously complete an open-ended questionnaire exploring their views on these aspects. Fifty-four patients and 40 caregivers gave their informed consent and participated in the survey. Fifty-three patients were adults, 28% suffering from Duchenne/Becker muscular dystrophy. Patients reported 269 comments on health care services provided during the pandemic, 132 (49%) concerning positive aspects and 137 (51%) negative aspects. The prompt restart of the rehabilitation therapies and the staff closeness over the pandemic were the practical aspects most frequently appreciated (46.9%), while closer family contacts and the perception of being able to rely on the Centre's constant support were the most cited psychological aspects (53.1%). Architectural barriers, difficulties in accessing public health services, economic difficulties, and lack of support from welfare and other agencies were the practical critical points most frequently reported (89%). In addition, social isolation, and loneliness due to fear of contagion were the most negative psychological aspects (10.1%). As regard the caregivers' views, participants reported 151 comments. Of these, 86 (56.9%) were positive and 65 (43.1%) were negative. Among the positive aspects, the psychological ones - such as closer family contacts, not feeling abandoned and counting on the constant Centre's professional support prevailed (53.5%). As for the negative aspects, most caregivers (92.6%) believe that the pandemic exacerbated their financial and bureaucratic difficulties, particularly in poorer families.

Mechanical ventilation in Duchenne muscular dystrophy: A pilot project in Ukraine.

BACKGROUND: Home mechanical ventilation (HMV) prolongs survival in patients with Duchenne muscular dystrophy (DMD) until ±35 years of age. This study evaluates the implementation of a HMV pilot project in children with DMD in Ukraine. METHODS: Children with DMD were invited to Kirovograd Regional Children's Clinical Hospital, Kropyvnytskyi, Ukraine, for 5 days' training with non-invasive ventilation. Donated equipment comprised second-hand Covidien PB560 ventilators from Belgium. Due to the absence of carbon dioxide pressure and pulse oximetry monitoring, indications for HMV included sleep-related symptoms, restrictive lung function test, loss of ambulation for more than 1 year, or age greater than 17 years. Master class lectures on HMV were conducted for Ukrainian doctors in conjunction with patient training. RESULTS: Twelve Ukrainian physicians took part in face-to-face master classes and 50 Ukrainian physicians participated in online master classes. Simultaneously, eight Duchenne inpatients, mean age 15.4 (SD: 1.8) years and body mass index 25.8 (SD: 4.0), were included in the study. All patients chose nasal masks and volume-pressure-assisted control mode. After 6 weeks, one patient stopped HMV, two others used HMV partially during sleep, and 5/8 used nocturnal HMV increasingly with few complaints. Follow up via phone call was organized after hospitalization. CONCLUSIONS: Implementation of HMV is feasible in DMD inpatients in Ukraine. In the short term, the Ukrainian parliament should recognize official centers for HMV, and define the funding policy of equipment for HMV, and its maintenance. Local distributors should deliver equipment for HMV and devices for monitoring carbon dioxide pressure and pulse oximetry in specialized centers for HMV.

Current care practices for patients with Duchenne muscular dystrophy in China.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has presented challenges in the care of patients with chronic diseases. We identified the challenges faced by Chinese patients with Duchenne muscular dystrophy (DMD) during the pandemic. METHODS: An online cross-sectional survey was conducted between March 27 and June 30, 2021. RESULTS: Of the 2105 valid questionnaire responses, 2,056 patients were from non-lockdown areas. In these areas, 42.8% reduced outside daily activities, 49.4% reduced rehabilitation service use, 39.7% postponed regular follow-ups, and 40.8% reported accelerated motor function decline. These figures generally increased for patients from lockdown areas-67.3% reduced outside daily activities, 44.9% reduced rehabilitation service use, 79.6% postponed regular follow-ups, and 55.1% reported accelerated motor function decline. Ambulation loss was most commonly reported in September and March before 2020; however, this trend was absent in 2020. Regarding the informed prices of disease-modifying drugs in Europe and the United States, 86.7% could afford a maximum of one-twentieth of the prices, 8.0% could afford one-tenth of the prices, and only 0.6% of the patients could afford the full prices. CONCLUSIONS: Implementation of standardized care for DMD in China is consistent with global practices, and the COVID-19 pandemic has affected the care of patients with chronic diseases worldwide, particularly in lockdown areas. Telemedicine is an effective model for providing healthcare to such patients. Healthcare workers should assist patients and establish more robust chronic disease management systems. Collaboration between governmental and non-governmental entities could address the cost of disease-modifying drugs in China and other developing countries.

Comparison of telerehabilitation versus home-based video exercise in patients with Duchenne muscular dystrophy: a single-blind randomized study.

INTRODUCTION: Patients with Duchenne muscular dystrophy (DMD) have lost their access to on-site rehabilitation due to the COVID-19 pandemic. Telerehabilitation can be a viable approach for these patients to protect their muscle strength and functional status. The aim of this study is to compare telerehabilitation with home-based video exercises. PATIENTS AND METHODS: Male, ambulatory DMD patients were randomized into telerehabilitation and video-exercise groups. Nineteen patients were included in the final analyses. Telerehabilitation consisted of live online exercises, while video exercise implemented a pre-recorded video as a home-based program. Both programs spanned 8 weeks, three times a week. Patients' muscle strength with a hand-held dynamometer, Quick Motor Function Test, North-Star Ambulatory Assessment (NSAA), 6-Minute Walk Test (6MWT) and Caregiver Burden were recorded before and after treatment. RESULTS: The 6MWT of the telerehabilitation group was391.26 ± 95.08 m before and387.75 ± 210.93 after treatment (p = 0.94) and 327.46 ± 103.88 m before treatment and313.77 ± 114.55 after treatment in video group (p = 0.63). The mean NSAA score of the telerehabilitation group were26.70 ± 8.04 before treatment and 25.20 ± 11.33 after treatment (p = 0.24). In the video group scores were 21.66 ± 6.65 before to 22.00 ± 8.61 after treatment (p = 0.87). There were no significant changes between groups at the end of the treatments. The telerehabilitation group's neck extension, bilateral shoulder abduction, and left shoulder flexion, bilateral knee flexion and extension, bilateral ankle dorsiflexion, and left ankle plantar flexion strength improved significantly and were better than the video group (p < 0.05 for all measurements). CONCLUSION: A telerehabilitation approach is superior in improving muscle strength than a video-based home exercise, but none of the programs improved functional outcomes in ambulatory patients with DMD.

Can Innovative Trial Designs in Orphan Diseases Drive Advancement of Treatments for Common Neurological Diseases?

Global regulatory agencies have transformed their approach to approvals in their processes for formal review of the safety and efficacy of new drugs. Opportunities for innovation have expanded because of the coronavirus disease 2019 (COVID-19) pandemic. Several regulatory-led initiatives have progressed rapidly during the past year, including patient-focused drug development, model-informed drug development, real-world evidence, and complex innovative trial designs. Collectively, these initiatives have accelerated the rate of approvals. Despite demands to focus on urgent needs imposed by the COVID-19 pandemic, the number of new drug approvals over the past year, particularly for rare diseases, has outpaced expectations. Advancing therapeutics for nervous system disorders requires adaptive strategies that align with rapid developments in the field. Three relentlessly progressive diseases, amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and Parkinson's disease are in urgent need of new treatments. Herein, we propose new regulatory initiatives, including innovative trial designs and patient-focused drug development that accelerate clinical trial conduct while meeting critical regulatory requirements for therapeutic approval.

Morbidity, Clinical Course and Vaccination against SARS-CoV-2 Virus in Patients with Duchenne Muscular Dystrophy: A Patient Reported Survey.

Background: Patients with Duchenne muscular dystrophy (DMD) may be at higher risk of a severe course of COVID-19. The aim of the study was to evaluate: (1) the incidence and course of COVID-19 infection in DMD patients; (2) the vaccination status of DMD patients; and (3) COVID-19 related anxiety among DMD families. Materials and Methods: The study was conducted during an online symposium for DMD patients and their families. All participants (DMD families; n = 150) were asked to fill in the online survey with questions about COVID-19 infection history, vaccination against SARS-CoV-2 and anxiety during pandemic. Results: 53 DMD patients filled in the survey. Five (9.43%) were COVID-19 positive with mild symptoms of respiratory infection and anosmia; 23 (42.6%) were vaccinated, but in almost 20% of DMD families, none of the family members was vaccinated. Respondents revealed anxiety related both to the vaccination procedure and to COVID-19 infection (complications after infection 93.6%, death 62.4% respondents). Changes in health care system organization also aroused concern among participants (85.3%). Conclusion: The course of the COVID-19 infection in DMD patients was mild. Not enough patients with DMD and their families are vaccinated. Education about the management of COVID-19 infections and the vaccination procedure for DMD patients is needed and expected.

Influence of A Public Health Emergency On Care For Patients With Duchenne Muscular Dystrophy: An Online, Cross-Sectional Survey (preprint)

Background: The public health emergency has created challenges for the care of patients, particularly those with chronic diseases such as Duchenne muscular dystrophy. To elucidate the challenges faced by Chinese patients with Duchenne muscular dystrophy during the public health emergency coronavirus disease 2019 pandemic, we conducted an online cross-sectional survey, the responses of which were collected between March 27 and June 30, 2021. Results: : In total, valid questionnaire responses were obtained from 2,105 patients, of whom 49 lived in pandemic lockdown areas. Of the 2,056 responders from non-lockdown areas, 42.8% reduced their outside daily activities, 49.4% reduced their use of rehabilitation services, 39.7% postponed regular follow-up appointments, and 40.8% complained of accelerated declines in motor function over the previous year. The corresponding figures for the 49 participants from lockdown areas were almost all higher, with 67.3% reducing outside daily activities, 44.9% reducing their use of rehabilitation services, 79.6% postponing regular follow-up appointments, and 55.1% complaining of accelerated declines in motor function. When asked whether they expected more assistance from society than they had received before the pandemic, 60.8% of patients in non-lockdown areas and 87.8% of those in lockdown areas responded affirmatively. When asked whether they felt more anxious than they had before the pandemic and needed psychological counseling, 11.5% of respondents in non-lockdown areas and 18.4% of respondents in lockdown areas responded affirmatively. In non-lockdown areas, 76% of respondents had at least one telemedicine visit, and 71% of them thought that telemedicine was helpful. In lockdown areas, 91.8% had used telemedicine at least once, and 66.7% of them found it helpful. Conclusions: : These public health emergency control measures have affected the care of patients with chronic diseases worldwide, particularly pronounced in lockdown areas. It is imperative that healthcare workers assist patients and establish more robust chronic disease management systems. Telemedicine is an effective model for providing healthcare to such patients.

Fully automated fast-flow synthesis of antisense phosphorodiamidate morpholino oligomers.

Rapid development of antisense therapies can enable on-demand responses to new viral pathogens and make personalized medicine for genetic diseases practical. Antisense phosphorodiamidate morpholino oligomers (PMOs) are promising candidates to fill such a role, but their challenging synthesis limits their widespread application. To rapidly prototype potential PMO drug candidates, we report a fully automated flow-based oligonucleotide synthesizer. Our optimized synthesis platform reduces coupling times by up to 22-fold compared to previously reported methods. We demonstrate the power of our automated technology with the synthesis of milligram quantities of three candidate therapeutic PMO sequences for an unserved class of Duchenne muscular dystrophy (DMD). To further test our platform, we synthesize a PMO that targets the genomic mRNA of SARS-CoV-2 and demonstrate its antiviral effects. This platform could find broad application not only in designing new SARS-CoV-2 and DMD antisense therapeutics, but also for rapid development of PMO candidates to treat new and emerging diseases.

A web-based questionnaire survey on the influence of coronavirus disease-19 on the care of patients with muscular dystrophy.

To clarify the influence of coronavirus disease-19 (COVID-19) on the care of muscular dystrophy patients, we performed a questionnaire survey that was posted on the internet on May 11, 2020. By the end of July 2020, 542 responses had been collected. Approximately 30% of patients postponed regular consultations, and one-quarter of patients who received consultation more than once a month used telephone consultations. Two of 84 patients with Duchenne muscular dystrophy had reduced their steroid doses. A shortage of ventilator accessories and infection protection equipment occurred following the onset of COVID-19, and this shortage had a serious impact on medical care and infection prevention measures. Reductions in rehabilitation and other services, and avoidance of outings, led to a decrease in exercise and an increase in caregiver burden. Inpatients were restricted from going out and visiting family members. More than 20% of patients reported physical or mental complaints; however, few required treatment. COVID-19 has seriously affected the activities and quality of life of patients with muscular dystrophy. We will continue this survey and analyze the longitudinal changes.

Is It Possible to Have Home E-Monitoring of Pulmonary Function in Our Patients with Duchenne Muscular Dystrophy in the COVID-19 Pandemic?-A One Center Pilot Study.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common, progressive, irreversible muscular dystrophy. Pulmonary function is crucial for duration of life in this disease. Currently, the European Respiratory Society is focused on digital health, seeking innovations that will be realistic for digital respiratory medicine to support professionals and patients during the COVID-19 pandemic. AIMS: The aim of this study was to investigate whether it is possible to monitor pulmonary function at home using an individual electronic spirometry system in boys with Duchenne muscular dystrophy. MATERIALS AND METHODS: In this observational, prospective study, conducted from March 2021 to June 2021, twenty boys with DMD (aged 8-16) were enrolled. The patients were recruited from the Rare Disease Centre, University Clinical Centre, of Gdansk, Poland. Medical history and anthropometric data were collected, and spirometry (Jaeger, Germany) was performed in all patients at the start of the study. Each patient received an electronic individual spirometer (AioCare) and was asked to perform spirometry on their own every day, morning and evening, at home for a period of 4 weeks. The number of measurements, correctness of performing measurements, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF) were evaluated. RESULTS: Finally, 14 out of 20 boys enrolled in the study with a mean age of 12.5 years (7 non-ambulatory) applied and received a home spirometer (AioCare). A total of 283 measurements were performed by all patients at home for 4 weeks. Half of the patients were able to perform measurements correctly. There were no significant differences between mean values of FVC, FE1, PEF between home and hospital spirometry (p > 0.05) expect PEF pv% (p < 0.00046). Patients with higher FEV1 (p = 0.0387) and lower BMI (p = 0.0494) were more likely to take home spirometer measurements. The mean general satisfaction rating of home-spirometry was 4.33/5 (SD 0.78), the mean intelligibility rating was 4.83/5 (SD 0.58). Reasons for irregular measurements were: forgetting (43%), lack of motivation (29%), difficulty (14%), lack of time (14%). CONCLUSION: Home electronic monitoring of pulmonary function in patients with DMD is possible to implement in daily routines at home. This protocol should be introduced as early as possible in patients 7-8 years old with good, preserved lung function. Patients accept this form of medical care but require more education about the benefits of e-monitoring. There is a need to implement a system to remind patients of the use of electronic medical devices at home, e.g., via SMS (short message service).

Discovering Spatial-temporal Patterns of COVID-19 Pandemic in South Korea: A Data-driven Approach using Dynamic Mode Decomposition (preprint)

A novel severe acute respiratory syndrome coronavirus 2 emerged in December 2019, and it took only a few months for WHO to declare COVID-19 as a pandemic in March 2020. It is very challenging to discover complex spatial-temporal transmission mechanisms. However, it is crucial to capture essential features of regional-temporal patterns of COVID-19 to implement prompt and effective prevention or mitigation interventions. In this work, we develop a novel framework of compatible window-wise dynamic mode decomposition (CwDMD) for nonlinear infectious disease dynamics. The compatible window is a selected representative subdomain of time series data, in which compatibility between spatial and temporal resolutions is established so that DMD can provide meaningful data analysis. A total of four compatible windows have been selected from COVID-19 time-series data from January 20, 2020, to May 10, 2021, in South Korea. The spatiotemporal patterns of these four windows are then analyzed. Several hot and cold spots were identified, their spatial-temporal relationships, and some hidden regional patterns were discovered. Our analysis reveals that the first wave was contained in Daegu and Gyeongbuk area but it spread rapidly to the whole of South Korea after the second wave. Later on, the spatial distribution is seen to become more homogeneous after the third wave. Our analysis also identifies that some patterns are not related to regional relevance. These findings have then been analyzed and associated with the inter-regional and local characteristics of South Korea. Thus, the present study is expected to provide public health officials helpful insights for future regional-temporal specific mitigation plans.

Respiratory Telerehabilitation of Boys and Young Men with Duchenne Muscular Dystrophy in the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic forced reorganization of the multidisciplinary healthcare system for Duchenne muscular dystrophy. Digital solutions seem to be optimal for providing rehabilitation at this time. The aim of this study was to investigate whether it is possible to conduct respiratory physical therapy with the use of telerehabilitation in Duchenne muscular dystrophy. METHODS: The study was conducted during an online conference for families with DMD. During the physical therapy panel we showed the video with the instructions of respiratory exercises. All participants (n = 152) were asked to fill in the online survey evaluating the quality, acceptance, and understanding of the instructions. RESULTS: The survey was filled in by 45 (29.6%) participants. The mean rating of satisfaction was 4.70/5, and for intelligibility was 4.78/5. Thirty-seven (82.2%) patients declared that they had performed the exercises, all caregivers declared that it was possible to perform the proposed exercises a few times a week or daily, and only two respondents replied to invitations to individual online sessions. CONCLUSIONS: Findings from the study show that respiratory telerehabilitation may be implemented for DMD patients; however, the interest in digital rehabilitation among caregivers of DMD boys in Poland is low. The reasons for this situation require further research.

Changes in motor function in Duchenne muscular dystrophy patients after travel restrictions due to COVID-19.

INTRODUCTION/AIM: This retrospective study aimed to quantify the changes in motor function in patients with Duchenne muscular dystrophy (DMD) due to the government-imposed travel restrictions associated with the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Twelve DMD patients were enrolled in this investigation (mean ± SD age: 9.8 ± 3.6 y). Their physical characteristics and motor function were evaluated approximately 3 mo before, immediately before, and approximately 3 mo after the travel restrictions were decreed. Statistical comparisons were performed of the changes in motor function before and after the travel restrictions. RESULTS: The change in range of motion (ROM) of ankle dorsiflexion was significantly decreased after the travel restrictions. Changes in body mass index and other motor function parameters were not significant. DISCUSSION: An apparent decrease in the amount of physical activity due to travel restrictions in response to COVID-19 negatively affected ankle dorsiflexion ROM but not other motor functions. A more sedentary lifestyle and lack of regular physical therapy services most likely contributed to this reduction. The use of remote rehabilitation tools with the involvement of physiotherapists may help mitigate such changes and prevent more severe physical decline.