| 1. |
- Michael, Eva, et al.
(författare)
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Long term treatment with ataluren-the Swedish experience
- 2021
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Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Ataluren is a relatively new treatment for male patients with Duchenne muscular dystrophy (DMD) due to a premature stop codon. Long-term longitudinal data as well as efficacy data on non-ambulant patients are still lacking. Here we present the results from a long-term follow-up study of all DMD patients treated with ataluren and followed at the Queen Silvia Children's Hospital in Gothenburg, Sweden, with focus on the evolution of patients' upper motor and respiratory function over time. Methods This is a retrospective longitudinal case-series study of all male DMD patients treated with ataluren and followed at the Queen Silvia Children's Hospital in Gothenburg, Sweden, since 2008. Results Our eleven patients had a median exposure to ataluren of 2312 days which is almost a fourfold higher than previous studies. Loss of ambulation occurred at a median age of 13.2 years. Patients who lost ambulation prior to 13.2 years of age had received ataluren for 5 years, whereas patients who continued to be ambulatory after 13.2 years of age had received ataluren for 6.5 years until loss of ambulation or last follow-up if still ambulatory. Four of six non ambulatory patients had Performance of the Upper Limb scores above the expected mean values over time. All but one patient maintained a pulmonary decline above the expected over time. All ambulatory patients increased in their predicted forced vital capacity (FVC) with 2.8 to 8.2% annually. Following loss of ambulation, 5 of 6 patients declined in predicted FVC (%), with annual rate of decline varying from 1.8 to 21.1%. The treatment was safe and well tolerated throughout the follow-up period. Conclusions This is the first study to present long-term cumulative treatment outcomes over a median period of 6.3 years on ataluren treatment. Our results indicate a delay in loss of ambulation, as well as a slower decline in FVC and upper limb motor function even after loss of ambulation. We suggest that treatment with ataluren should be initiated as soon as the diagnosis is confirmed, closely monitored and, in case of sustainable benefit, continued even after loss of ambulation.
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| 2. |
- Olsson, Bob, 1969, et al.
(författare)
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NFL is a marker of treatment response in children with SMA treated with nusinersen
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:9, s. 2129-2136
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Tidskriftsartikel (refereegranskat)abstract
- Background Recently, the anti-sense oligonucleotide drug nusinersen was approved for spinal muscular atrophy (SMA) and our aim was to find a response marker for this treatment. Methods Twelve children with SMA type 1 and two copies of the SMN2 gene were included in a consecutive single-center study. The children were sampled for CSF at baseline and every time nusinersen was given intrathecally. The neuronal biomarkers NFL and tau and the glial biomarker GFAP were measured. Motor function was assessed using CHOP INTEND. Eleven similarly aged children, who were investigated to rule out neurological or infectious disease, were used as controls. Results Baseline levels of NFL (4598 +/- 981 vs 148 +/- 39, P = 0.001), tau (939 +/- 159 vs 404 +/- 86, P = 0.02), and GFAP (236 +/- 44 vs 108 +/- 26, P = 0.02) were significantly higher in SMA children than controls. Motor function improved by nusinersen treatment in median 13 points corresponding to 5.4 points per month of treatment (P = 0.001). NFL levels typically normalized ( < 380 pg/ml) between the fourth and fifth doses [- 879.5 pg/mL/dose, 95% CI (- 1243.4, - 415.6), P = 0.0001], tau levels decreased [- 112.6 pg/mL/dose, 95% CI (- 206-7, - 18.6), P = 0.01], and minor decreases in GFAP were observed [- 16.9 pg/mL/dose, 95% CI (- 22.8, - 11.2), P = 0.02] by nusinersen treatment. Improvement in motor function correlated with reduced concentrations of NFL (rho = - 0.64, P = 0.03) and tau (rho = - 0.85, P = 0.0008) but not GFAP. Conclusions Nusinersen normalized the axonal damage marker NFL and correlated with motor improvement in children with SMA. NFL may, therefore, be a novel biomarker to monitor treatment response early in the disease course.
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| 3. |
- Wahlgren, Lisa, 1980, et al.
(författare)
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One in five patients with Duchenne muscular dystrophy dies from other causes than cardiac or respiratory failure
- 2022
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:2, s. 147-156
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Tidskriftsartikel (refereegranskat)abstract
- Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder with increasing life expectancy from late teens to over 30 years of age. The aim of this nationwide study was to explore the prevalence, life expectancy and leading causes of death in patients with DMD in Sweden. Patients with DMD were identified through the National Quality Registry for Neuromuscular Diseases in Sweden, the Swedish Registry of Respiratory Failure, pathology laboratories, neurology and respiratory clinics, and the national network for neuromuscular diseases. Age and cause of death were retrieved from the Cause of Death Registry and cross-checked with medical records. 373 DMD patients born 1970-2019 were identified, of whom 129 patients deceased during the study period. Point prevalence of adult patients with DMD on December 31st 2019 was 3.2 per 100,000 adult males. Birth prevalence was 19.2 per 100,000 male births. Median survival was 29.9 years, the leading cause of death being cardiopulmonary in 79.9% of patients. Non-cardiopulmonary causes of death (20.1% of patients) mainly pertained to injury-related pulmonary embolism (1.3 per 1000 person-years), gastrointestinal complications (1.0 per 1000 person-years), stroke (0.6 per 1000 person-years) and unnatural deaths (1.6 per 1000 person-years). Death from non-cardiopulmonary causes occurred at younger ages (mean 21.0 years, SD 8.2; p = 0.004). Age at loss of independent ambulation did not have significant impact on overall survival (p = 0.26). We found that non-cardiopulmonary causes contribute to higher mortality among younger patients with DMD. We present novel epidemiological data on the increasing population of adult patients with DMD.
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