Abstract

Introduction. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease linked to the X chromosome caused by the lack of functional dystrophin. About 10-15% of cases are caused by nonsense mutations, and their natural history is thought to be similar to DMD by other causes. Ataluren is a new therapeutic option that promotes the readthrough of nonsense mutations leading to the production of functional dystrophin proteins.

Objective. To describe the natural history of patients with nonsense mutations DMD (nmDMD) and evaluate the impact of corticosteroids and ataluren on disease progression.

Methods. It is a retrospective, longitudinal case-series study of all male patients with nmDMD treated at Sant Joan de Déu Hospital in Barcelona, Spain, since 2007.

Results. 28 patients from 3.7 to 22 years old were included. The mean age at symptom onset was 3.5 years, and at genetic diagnosis was 4.5 years. All patients were treated with corticosteroids, and 17 patients also received ataluren. Patients treated with ataluren delayed the loss of ambulation by three years (14 vs 10.9 years). No patients treated with ataluren required non-invasive ventilation.

Conclusions. Patients with DMD caused by nonsense mutations present a similar phenotype to those with DMD with other types of mutations. Patients treated with ataluren delayed the loss of ambulation and appeared to maintain upper limb and respiratory function better than those not treated with ataluren.

Introduction

Duchenne muscular dystrophy (DMD) is a severe, X-linked, progressive neuromuscular disorder that primarily affects males and is characterised by progressive proximal muscle weakness, pseudohypertrophy of the calf muscles, and significantly elevated blood creatine kinase (CK) levels, which can serve as an early diagnostic marker 1,2. The initial symptoms, typically manifesting between 2 and 3 years of age, include difficulties with climbing stairs, a waddling gate, Gower’s sign (use of the hands to “walk” up on the limbs to stand up from a squatting position), and frequent falls. Affected children exhibit a gradual physical deterioration with increasing loss of strength and acquired abilities, often leading to the loss of ambulation around 10-12 years of age and needing assisted ventilation around 20 years of age. Even with optimal care and management of complications, most patients with DMD die between 20 and 40 years of age, with cardiac and respiratory complications as the leading causes of mortality 2,3.

Currently, there is no cure for DMD, even though multidisciplinary management of the symptoms with medical, surgical, and rehabilitative treatments can slow the natural course of the disease and improve the quality of life and longevity of the patients 1,3.

The primary therapeutic approach focuses on managing symptoms and slowing disease progression by using oral glucocorticoids. These drugs, such as prednisone and deflazacort, have shown efficacy in preserving motor function, delaying the loss of ambulation and the onset of cardiomyopathy, and reducing the need for scoliosis surgery. However, they do not halt disease progression and are associated with significant side effects, including weight gain, hypertension, osteoporosis, cataracts, and behavioural issues 1-4. Alternative steroids such as vamorolone have also demonstrated improvements in motor function and offer a better safety profile 1,5.

Complementing glucocorticoid therapy, early rehabilitation is crucial for maintaining physical functionality. Rehabilitation strategies typically include physiotherapy, occupational therapy, and psychosocial interventions and require a complete understanding of the DMD course and the individual goals to optimize quality of life 3,4. These therapies aim to delay complications such as contractures, scoliosis, loss of function, respiratory muscle weakness, and other irreversible musculoskeletal changes. Once a diagnosis is confirmed it is necessary the multidisciplinary rehabilitation assessment of motion, muscle extensibility, posture and alignment, strength, respiratory function, cardiac manifestations, quality of life, and participation in daily living normal activities, and the periodical reassessment (usually every 6 to 12 months) to adapt the therapeutic strategies to the evolving needs of the patient 1,4.

The DMD is caused by mutations in the dystrophin gene, causing the loss of the dystrophin protein expression, a cell membrane protein involved in maintaining muscle integrity. About 10-15% of DMD cases result from nonsense mutations that introduce premature stop codons into the dystrophin gene, truncating the protein translation and leading to the production of nonfunctional and unstable dystrophin proteins. The lack of functional dystrophin causes plasma membrane leakage and muscle fibre degeneration, severely compromising muscle fibre integrity and accelerating disease progression 3,6,7.

In the last years, new therapy approaches focused on restoring dystrophin protein production, such as readthrough of nonsense mutations, have been explored 8. Ataluren is a mutation-specific therapy that is able to bypass nonsense mutations. It is a small, non-aminoglycoside molecule that promotes ribosomal readthrough of premature stop codons in mRNA, allowing for the production of functional dystrophin proteins 9,10.

Results from clinical studies have demonstrated the efficacy and safety of ataluren, particularly when initiated early in the disease course 9,10. Evidence shows that ataluren slows down the disease progression by slowing down the decline in motor function, extending the period of ambulation, and preserving respiratory and upper limb function 7,11. Recognizing its potential, in 2014, the European Medicines Agency (EMA) granted ataluren with conditional marketing authorization for the treatment of ambulatory male patients aged ≥2 years with DMD resulting from a nonsense mutation in the dystrophin gene (https://www.ema.europa.eu/en/medicines/human/EPAR/translarna) 3,8.

The natural history and health burden of DMD caused by nonsense mutations (nmDMD) is thought to be similar to DMD from other causes7. The main objective of the study was to describe the natural history of patients with nmDMD and evaluate the impact of treatment modalities, particularly ataluren and corticosteroids, on disease progression. By leveraging the extensive clinical data collected over a decade, this study aims to provide valuable insights into the management and outcomes of patients with nmDMD.

Materials and methods

This retrospective, longitudinal case-series study was conducted at Sant Joan de Déu Hospital in Barcelona, Spain. It includes the revision of all male patients with nmDMD who had been followed up at the hospital for 200 months, from 2007 to 2024, with no restriction by age. From each patient, we obtained the age at DMD symptoms onset, age at genetic diagnosis, treatments, age at initiation of the different therapies, clinical manifestations of the disease, age at loss of ambulation, and need for non-invasive ventilation. We also obtained data on the motor function assessed using the 6MWT for all patients: however, it was not always possible to obtain data on the North Star Ambulatory Assessment (NSAA) score and upper limb power test (PUL) 2.0 score.

This is a descriptive study, and only qualitative data (i.e., mean, standard deviation, range) will be shown.

Before any data was collected, ethics committee approval and written informed consent for data collection procedures from the patient or his parent/legal guardian were obtained. The study has been conducted according to the ethical principles outlined in the Declaration of Helsinki, applicable privacy laws, and local regulations for each participating site, as well as with the Guidelines for Good Pharmacoepidemiology Practices.

Results

Study Population and Patient Characteristics

The study population included 28 male patients with genetically confirmed nmDMD who were followed up at Sant Joan de Déu Hospital between 2007 and 2024, with a mean follow-up time of 17 years.

The age of the patients included in the study at enrolment ranged from 3.7 to 22 years, providing a comprehensive view of the disease course from early childhood to young adulthood. The mean age of patients at symptom onset was 3.5 years, with a delay in genetic diagnosis observed at an average age of 4.5 years (Tab. I).

The cohort was characterised by point mutations leading to nonsense-mediated dystrophin deficiency, and all patients exhibited the hallmark features of DMD, including delayed motor milestones, difficulty rising from the floor (Gowers’ sign), and pseudohypertrophy of the calf muscles. The disease progressed predictably, with most patients experiencing a gradual decline in motor function and the eventual loss of ambulation.

Rehabilitation and Physiotherapy

All patients underwent standardized rehabilitation and physiotherapy based on their clinical condition. The goal was to preserve muscle strength and prevent physical complications. Therapies were tailored to individual needs, ensuring optimal recovery. Regular assessments were conducted to monitor progress and adjust treatments accordingly.

Steroid Therapy

Steroid treatment was the cornerstone of the management of the entire cohort. Of the 28 patients, 10 were initially prescribed deflazacort, while the remaining 18 began treatment with prednisone. The doses used were those recommended for patients with DMD (deflazacort 0.9 mg/kg/day and prednisone 0.7 mg/kg/day). The average age at the initiation of corticosteroid therapy was 5.5 years, consistent with current clinical guidelines recommending early treatment to delay disease progression (Tab. I). All patients continued corticosteroid therapy until transitioning to adult care, with none discontinuing treatment during the study period.

Scoliosis and Orthopedic Outcomes

Scoliosis is a common and debilitating complication of DMD, particularly in non-ambulatory patients. In this cohort, only four patients developed severe scoliosis that required surgical intervention (performed at the age of 15 years). The remaining patients maintained spinal stability.

Ataluren treatment

Among the 28 patients diagnosed with nmDMD, 17 received treatment with ataluren, while 11 did not. Seven out of the 17 patients treated with ataluren (41.2%) discontinued the treatment after they experienced the loss of ambulation. All patients received corticosteroid treatment, according to the established protocol, with either deflazacort or prednisone at the doses established for patients with DMD.

The patients who received ataluren initiated the treatment at a mean age of 7.2 years, ranging from 7.1 to 7.9. The delay in the loss of ambulation observed in the 6MWT was longer than in the group not treated with Ataluren (Fig. 1A). The mean age at loss of ambulation was 14 years, ranging from 7.8 to 19.3 years, in the ataluren treatment group, while the group of 11 patients who did not receive ataluren presented a mean age at loss of ambulation of 10.9 years (range 7.2 to 16.8 years) (Fig. 1B). There were no significant differences between groups in age at symptom onset, age at diagnosis, or age at initiation of corticosteroids (Tab. II). However, patients treated with ataluren lost ambulation significantly later than untreated patients (14.0 ± 2.3 vs. 10.9 ± 2.4 years, p = 0.0028).

Non-invasive ventilation in patients with nmDMD

As of the last follow-up, none of the patients treated with ataluren required non-invasive ventilation, while three patients not treated with ataluren required non-invasive ventilation. All three patients were over 20 years old when non-invasive ventilation was initiated.

NSAA scores in patients with nmDMD

The NSAA is a validated tool used to monitor disease progression and response to treatment in ambulant patients with DMD. This score ranges from 0 to 34 and reflects the ambulatory and functional abilities of the patients, with a higher score indicating better motor performance and lower scores highlighting reduced ambulatory function and greater challenges in performing daily activities 12.

Unfortunately, individual NSAA data were not consistently available for all patients; however, at the time of the last follow-up, the mean NSAA score for the patients treated with ataluren was 25, and for those who did not receive ataluren, it was 22.

PUL 2.0 scores in patients with nmDMD

The PUL 2.0 score is a standardised tool designed to assess upper limb function in patients with progressive neuromuscular disorders, such as DMD. It evaluates motor abilities across different functional domains, including shoulder, elbow, and wrist movements, with a maximum score of 42 indicating full functionality. The score is particularly useful for monitoring the progression of upper limb involvement and the effectiveness of treatments in maintaining upper limb mobility13. Unfortunately, individual PUL scores were not consistently available for all patients; however, the mean PUL 2.0 available score was 25 in the group of patients receiving ataluren and 20 in the group of patients not treated with ataluren (n = 5) at the time of the last follow-up.

Discussion

DMD is a severe form of muscular dystrophy characterised by the progressive muscle weakness that begins in early childhood. This condition usually leads to loss of ambulation in the second decade of life, the need for ventilation support in early adulthood, and cardiac and respiratory complications that lead to death between 20 and 40 years of age 3,14.

Even though DMD can be caused by multiple types of mutations, such as deletions, duplications, skip, and nonsense mutations, the natural history is thought to be similar, regardless of the genetic cause of the disease 15,16.

In this paper, we report the natural history of 28 patients with nmDMD and compare their clinical characteristics based on whether they use ataluren, a mutation-specific therapy that promotes the readthrough of nonsense mutations, in addition to corticosteroids.

Our patient population presented a mean age at symptom onset of 3.5 years; however, the genetic diagnosis was delayed until 4.5 years of age on average. This diagnostic delay underscores the importance of early genetic testing and awareness of DMD symptoms among healthcare providers to facilitate timely intervention.

All patients exhibited delayed motor milestones, Gowers’ sign, and pseudohypertrophy of calf muscles, with expected disease progression alongside a gradual decline in motor function and loss of ambulation in most cases.

Phenotypic Similarity Across DMD Mutations

The patients of our study, all nmDMD, exhibit a phenotype that is largely similar to patients with other types of DMD mutations. This highlights the uniformity of clinical progression, irrespective of the underlying genetic cause, particularly in the absence of targeted treatments 16. Such similarity underscores the shared pathophysiological mechanisms driving muscle degeneration in DMD, including disruptions in dystrophin synthesis, inflammation, and fibrosis3. Despite genetic differences, these patients face comparable timelines for motor decline and respiratory challenges, which simplifies treatment comparisons across subgroups. This phenotypic uniformity provides a crucial foundation for clinical trials and studies of therapies like ataluren, enabling researchers to assess outcomes broadly without requiring separate stratification for different mutation types. Moreover, it reinforces the need for universal standards of care to address the shared challenges posed by this debilitating disease.

Delay of complications with steroids

The current standard of care for DMD is based on the use of glucocorticoids such as deflazacort or prednisone 14. It has been recognised that the long-term use of corticoids may alter the natural history of DMD by improving motor function, slowing down the development of scoliosis and the need for scoliosis surgery, improving pulmonary and cardiac function, and improving the quality of life 17,18.

All patients in our study received early treatment with steroids, which were initiated at 5.5 years of average age, and only four patients required scoliosis surgery. The early initiation and consistent use of steroid therapy, combined with regular physiotherapy to preserve posture and prevent musculoskeletal deformities, likely contributed to the delayed onset of complications such as scoliosis and respiratory decline, highlighting their critical role in managing DMD. These findings underscore the importance of comprehensive orthopedic management and proactive monitoring in preventing scoliosis and its associated complications.

Impact of Ataluren on Ambulation

Even though steroids combined with rehabilitative treatments slow down the disease progression and improve patients’ quality of life, these approaches do not target the underlying cause of the disease 9. On the contrary, ataluren is a small molecule that promotes therapeutic nonsense suppression, restoring the expression of full-length functional dystrophin protein in DMD 9,10. Clinical trials and real-world data have demonstrated that ataluren is safe, effectively delays disease progression, and benefits ambulatory and non-ambulatory patients 9,10,19,20.

Our observations are consistent with existing evidence21. In our study, although data were not available for all patients, we observed that patients treated with ataluren lost ambulation at a mean age of 14 years, while patients not treated with ataluren lost the ambulation at 10.9 years on average, thus suggesting that ataluren may contribute to prolonged mobility.

The introduction of ataluren in patients with nmDMD appears to significantly delay the loss of ambulation by an average of three years compared to untreated patients. This is a critical milestone in managing DMD as prolonged ambulation leads to a better quality of life and delays the onset of complications associated with non-ambulatory stages, such as scoliosis and respiratory comorbidities 22.

The extended ability to walk highlights the potential of ataluren for delaying disease progression by targeting the underlying genetic defect and restoring partial dystrophin production. This delay also has psychological and social benefits for patients and their families, as ambulation is closely tied to independence 23. These findings strongly support ataluren as a viable option for maintaining motor function in this specific subgroup of DMD patients, emphasizing the need for its broader implementation in clinical practice.

Moreover, the NSAA score was slightly higher in the patients treated with ataluren (25 vs 22), suggesting that patients treated with ataluren maintained a relatively good level of mobility and motor functions despite the progressive nature of the disease. The difference in scores between treated and untreated groups suggests that ataluren may have a protective effect in slowing the functional decline associated with DMD. Regular assessments using the NSAA are critical for tracking therapeutic outcomes, providing valuable data on how ataluren may impact the long-term preservation of motor skills. However, variability in patient response highlights the need for further research to optimize treatment strategies and evaluate their sustained efficacy over time.

Preservation of Respiratory and Upper Limb Function

In addition to its impact on ambulation, ataluren has demonstrated a notable advantage in preserving respiratory and upper limb function in treated patients compared to untreated individuals 19,24. This is particularly significant as the maintenance of these functions directly correlates with prolonged independence and reduced healthcare burdens and complications in the advanced stages of DMD 25,26. The preservation of respiratory function results in a delayed need for invasive interventions such as mechanical ventilation, while upper limb functionality supports daily activities, communication, and autonomy. Moreover, respiratory function preservation is clinically important as respiratory failure is one of the main causes of death in DMD 19,27.

In our study, we observed that none of the patients treated with ataluren required non-invasive ventilation, highlighting the potential efficacy of the treatment in managing respiratory complications. Among the patients treated with ataluren, there were two individuals over 20 years old, with acceptable upper extremity function to perform daily activities and no need for noninvasive ventilation. This finding contrasts with the outcomes observed in untreated patients, where the need for ventilation was more prevalent.

Likewise, a mean PUL 2.0 score value of 25 was found in patients treated with ataluren where the data was available, suggesting moderate upper limb functionality, highlighting a potential therapeutic benefit in slowing functional decline, while the patients not treated with ataluren presented a lower level of upper limb functionality (PUL 2.0 score = 20). The PUL 2.0 score is an important tool for assessing upper limb performance in patients with neuromuscular disorders, particularly in non-ambulatory stages, where maintaining arm and hand function is critical for daily activities and greatly impacts quality of life and independence 27. The lower mean score observed in untreated patients shows the potential of ataluren in slowing the progression of functional decline. However, variability in scores among individuals points out the need for further research to optimize treatment strategies and assess long-term outcomes. The PUL 2.0 remains an essential tool in both clinical practice and research settings.

The benefit of preserving respiratory and upper limb function further highlights the therapeutic potential of ataluren in addressing critical aspects of disease progression that directly impact patient outcomes. Continued monitoring of these parameters in clinical trials will strengthen the evidence base for ataluren’s efficacy and may guide refinements in its use to maximize patient benefits over the disease trajectory.

Importance of Understanding Natural History

A comprehensive understanding of the natural history of each DMD patient is essential for accurately assessing the impact of specific treatments like ataluren. Natural history data provide critical benchmarks for evaluating whether interventions effectively alter the disease course. Without this contextual knowledge, interpreting clinical outcomes becomes challenging, particularly given the variability in disease progression between individuals. Longitudinal studies capturing the natural progression of motor, respiratory, and upper limb functions in untreated patients are therefore vital 4. They serve as control data for assessing the therapeutic impact of ataluren and other emerging treatments 18. Additionally, understanding natural history helps to establish realistic expectations for patients and caregivers while facilitating the development of more targeted therapies tailored to individual needs 23. In this context, ataluren’s demonstrated ability to improve key outcomes represents a significant step forward, but ongoing research is needed to optimize its role within a broader treatment framework.

This study highlights the critical role of timely intervention and multidisciplinary care in the management of DMD. The data from Sant Joan de Déu Hospital demonstrates that consistent steroid therapy, combined with early rehabilitation, can delay disease progression and mitigate complications such as scoliosis. However, the introduction of ataluren offers a promising therapeutic option for patients with nmDMD, addressing the underlying genetic defect and preserving motor and respiratory function. Continued research and longitudinal studies are essential to further understand the natural history of nmDMD and optimize treatment strategies to improve patient outcomes and quality of life.

Conclusions

The non-availability of some parameters such as NSAA, PUL and vital capacity for all patients could constitute a limitation of the study. However, patients treated with ataluren lost ambulation on average 3 years later than untreated patients and appeared to maintain better respiratory and upper limb function.

To be noted that on March 28, 2025 the European Commission decided not to renew the conditional marketing authorization for ataluren (Translarna) in the European Union. This decision highlights the need for continued collection of real-world evidence on the efficacy and safety of the drug and underlines the importance of ongoing research efforts to validate its clinical benefit. Understanding the natural history of each patient remains essential for objectively assessing the impact of specific treatments.

Acknowledgements

The authors would like to thank Iria Nieto Vázquez, Mercè Vallribera Relaño, and Elvira Nieto for their continued support.

Funding

The project was funded by PTC-Therapeutics International Limited with a research grant for the Investigational Project “Cohort of Spanish Patients with Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)”.

Conflict of interest statement

Carlos Ortez and Andrés Nascimento has received speaker fees from Novartis, PTC Therapeutics, Roche and Sarepta Therapeutics, and is an investigator on clinical trials related to DMD, sponsored by Italfarmaco S.p.A., PTC Therapeutics, Roche, and Sarepta Therapeutics.

The rest of the authors declare that they have no competing interests, except for the funding received from PTC-Therapeutics International Limited to support this research project.

Authors contributions

A.N., J.E., L.C., J.A., and C.O. performed the clinical examination of patients and interpreted the results. J.A. and C.O. were responsible for sample collection and data analysis. J.A. and C.O. conducted the statistical analysis and designed the figures. A.N. and C.O. contributed to the analysis and interpretation of results. A.N. and C.O. designed the study and participated in data analysis. All authors contributed to the writing of the manuscript, read, and approved the final version.

Ethical consideration

This study was performed under the approval of the local Ethics Committee (Comité Ético de Investigación Clínica Fundació Sant Joan de Déu; PIC-16-15) and conducted according to the Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study.

History

Received: April 8, 2025

Accepted: Septermber 17, 2025

Figures and tables

Figure 1. (A). Graphical representation of the 6-minute walk test (6MWT) during the study period of the patients (grey: patients not treated with ataluren; green: patients treated with ataluren); (B). Boxplot of the age at loss of ambulation according to the use of ataluren. The boxes represent 25th, 50th, and 75th percentiles, whiskers extend from the largest data ≤1.5 times the interquartile range (IQR) to the smallest data ≥1.5 IQR, and outliers are the values outside this range. Patients treated with ataluren lost ambulation significantly later than untreated patients (p = 0.0028).

Patient Age of onset (y) Age at diagnosis (y) Nonsense mutation Steroids use Age at start of Steroids (y) Ataluren Age at start of ataluren (y) Loss of ambulation (y)
1 4.2 4.9 Exon 42: c.5935G > T; p.Glu1979* y 5.7 n n/a 11
2 4.3 4.7 Exon 43: c.6286C > T. p.GLN2096* y 5.5 n n/a 11.5
3 3.8 4.5 Exon 66: c.9568C > T; p.Arg3190* y 5.3 n n/a 11.8
4 3.7 4.2 Exon 55: c.8038C > T. p.Arg2680* y 5.5 n n/a 7.2
5 3.5 4 Exon 76: c.10801C > T; p.Gln3601* y 4.5 n n/a 10.9
6 3.8 4.5 Exon 74: c.10425C > A. p.Tyr3475* y 6 n n/a 10.4
7 3.9 5 Exon 35: c.4996C > T: p.Arg166* y 5.3 n n/a 16.8
8 4.5 5.2 Exon 13: c.1501G > T; p.Glu501* y 5.6 n n/a 11.1
9 3.9 4.7 Exon 54: c.7899G > A. p.Trp2366* y 5.9 n n/a 11.3
10 3.8 4.3 Exon 51: c.7436G > A; p.Trp2479* y 5.9 n n/a 9
11 4.4 5.6 Exon 19: c.2353C > T. p.Gln785* y 6.2 n n/a 8.9
Mean ± SD (No Ataluren) 4.0 ± 0.3 4.7 ± 0.5 y 5.6 ± 0.5 n n/a 10.9 ± 2.4
12 4.2 4.9 Exon 16: c.1990C > T. p.Gln664* y 5.7 y 7 7.8
13 3.1 4 Exon 31: c.4271T > A; p.Leu1424* y 5.2 y 7.2 14
14 3.1 3.8 Exon 40: c.5676C > A; p.Cys1892* y 5.2 y 7.2 14.6
15 4 4.7 Exon 70: c.10109C > T; pArg3370* y 5.8 y 7.3 13.7
16 3.7 4.1 Exon 55: c.8038C > T; p.Arg2680* y 5 y 7 15.2
17 3.8 4.2 Exon 3: c.133C > T; p.Gln45* y 5.2 y 7.5 14.2
18 4.3 4.9 Exon 3: c.133C > T; p.Gln45* y 5.7 y 7.3 13.2
19 3.9 4.6 Exon 11: c.1286C > G. p.Ser429* y 5.3 y 7.9 14.2
20 3.7 4.3 Exon 35: c.4996C > T: p.Arg166* y 4.8 y 7 19.3
21 4.3 4.9 Exon 13: c.1501G > T. p.Glu501* y 6 y 7.2 14.3
22 3.6 4.2 Exon 5: c.353G > A; p.Trp118* y 5.7 y 7.1 15
23 3.1 3.8 Exon 5: c.335G > A p.Trp112* y 5 y 7 14.1
24 4 4.6 Exon 5: c.335G > A p.Trp112* y 5 y 7.2 14.3
25 3.9 4.6 Exon 8: c.693C > A. p.Tyr231* y 6 y 7.1 12.9
26 3.4 4.1 Exon 36: c.5131C > T p.Gln1711* y 5.9 y 7.1 15
27 3.5 4.2 Exon 34 c.4838G > A;p.Trp1632* y 5.2 y 7 15.3
28 3.9 4.5 Exon 23: c.3049A > T; p.Lys1017* y 5.9 y 7.3 10.9
Mean ± SD (Ataluren) 3.7 ± 0.4 4.4 ± 0.4 y 5.4 ± 0.4 y 7.2 ± 0.2 14.0 ± 2.3
Table I. Characteristics of the patients enrolled in the study.
No Ataluren (n = 11) Ataluren (n = 17) p-value
Age of onset (y) 4.0 ± 0.3 3.7 ± 0.4 0.081
Age at diagnosis (y) 4.7 ± 0.5 4.4 ± 0.4 0.075
Age at start of corticoids (y) 5.6 ± 0.5 5.4 ± 0.4 0.437
Loss of ambulation (y) 10.9 ± 2.4 14.0 ± 2.3 0.0028
Values are mean ± SD; Student’s t-test (independent samples).
Table II. Comparison of baseline characteristics and loss of ambulation between patients treated and not treated with ataluren (Student’s t-test).

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Carlos Ortez - Neuromuscular Diseases Unit, Hospital Sant Joan de Déu, Barcelona, Spain https://orcid.org/0000-0001-8187-8103

Andrés Nascimento - Neuromuscular Diseases Unit, Hospital Sant Joan de Déu, Barcelona, Spain https://orcid.org/0000-0003-4952-5732

Jesús Armijo - Neuromuscular Diseases Unit, Hospital Sant Joan de Déu, Barcelona, Spain https://orcid.org/0000-0001-7618-5564

Jésica Expósito - Neuromuscular Diseases Unit, Hospital Sant Joan de Déu, Barcelona, Spain https://orcid.org/0000-0002-6233-823X

Laura Carrera - Neuromuscular Diseases Unit, Hospital Sant Joan de Déu, Barcelona, Spain https://orcid.org/0000-0003-4762-7591

Daniel Natera-de Benito - Neuromuscular Diseases Unit, Hospital Sant Joan de Déu, Barcelona, Spain https://orcid.org/0000-0001-7764-2085

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Ortez, C., Nascimento, A. ., Armijo, J., Expósito, J., Carrera, L., & Natera-de Benito, D. (2025). Natural history of patients with nonsense mutation Duchenne muscular dystrophy treated with ataluren in Spain. Acta Myologica, 44(3). https://doi.org/10.36185/2532-1900-1219
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