Publications by authors named "Erik H Niks"
This study investigated if structural variation in specific gray matter areas is associated with corticosteroid treatment or genotype, and if cerebral morphological variations are related to neuropsychological and behavioral outcomes. The CAT12 toolbox in SPM was used for MRI segmentations, assessing subcortical structures, cortical thickness, gyrification, and sulci depths for DMD patients (n = 40; 9-18 years) and age-matched controls (n = 40). Comparisons were made between DMD vs.
View Article and Find Full Text PDFDuchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder caused by the absence of functional dystrophin protein. In addition to muscle, dystrophin is expressed in the brain in both neurons and glial cells. Previous studies have shown altered white matter microstructure in patients with DMD using diffusion tensor imaging (DTI).
View Article and Find Full Text PDFEvaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e.
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- This study analyzed the functional changes in children and adolescents with Duchenne muscular dystrophy (DMD) as they transition from being able to walk to losing that ability (loss of ambulation, or LoA) to improve clinical trial designs for new treatments.
- It included 51 participants aged 7 to 18 and assessed metrics like pulmonary function and upper limb performance before and after LoA, noting that significant declines often occurred before losing ambulation.
- The findings suggest that clinical trials could include patients showing early signs of decline in function, and that a varied sequence of functional loss among patients indicates the need for more comprehensive methods to evaluate treatment effectiveness.
Article Synopsis
- Duchenne muscular dystrophy (DMD) is a serious genetic disorder caused by a lack of dystrophin, and the study explores the potential of givinostat, a histone deacetylase inhibitor, to improve outcomes for affected children.* -
- Conducted as a phase 3, double-blind, placebo-controlled trial across 41 sites in 11 countries, researchers tested the safety and efficacy of givinostat in boys aged 6 and older who were already on corticosteroid treatment.* -
- The primary goal was to assess the four-stair climb performance after 72 weeks of treatment, comparing changes between those given givinostat and the placebo, while monitoring safety throughout the study.*
Article Synopsis
- Vamorolone, a glucocorticoid receptor agonist, was tested to assess its effectiveness and safety over 48 weeks compared to prednisone in children with Duchenne muscular dystrophy (DMD).
- A double-blind clinical trial involved 121 participants aged 4 to under 7 years, receiving varying doses of vamorolone and prednisone, with improvements monitored in motor skills and growth.
- Results indicated that vamorolone (6 mg/kg/day) maintained motor skill improvements over 48 weeks, with significant growth benefits seen after participants switched from prednisone to vamorolone.
Background: Shortening of the long finger flexors (Flexor Digitorum Profundus, FDPs) in Duchenne Muscular Dystrophy (DMD) causes reduced hand function. Until now, longitudinal studies on the natural course of the shortening of the FDPs are lacking, which impedes recommendations on timing and evaluation of preventive measures.
Objective: To investigate the longitudinal course of the FDP length during different disease stages focusing on symmetry, timing, and decline of the FDP length.
Objective: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI).
View Article and Find Full Text PDFBackground: Becker muscular dystrophy (BMD) is an X-linked disorder characterized by slow, progressive muscle damage and muscle weakness. Hallmarks include fibre-size variation and replacement of skeletal muscle with fibrous and adipose tissues, after repeated cycles of regeneration. Muscle histology can detect these features, but the required biopsies are invasive, are difficult to repeat and capture only small muscle volumes.
View Article and Find Full Text PDFMuscle biopsies are used in clinical trials to measure target engagement of the investigational product. With many upcoming therapies for patients with facioscapulohumeral dystrophy (FSHD), the frequency of biopsies in FSHD patients is expected to increase. Muscle biopsies were performed either in the outpatient clinic using a Bergström needle (BN-biopsy) or in a Magnetic Resonance Imaging machine (MRI-biopsy).
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- The North Star ambulatory assessment (NSAA) is a key measure for tracking motor function in boys with Duchenne muscular dystrophy (DMD), but the minimal clinically important difference (MCID) for NSAA is not well-established, complicating result interpretation.
- This study aimed to estimate the MCID for NSAA using various methods, including statistical approaches and patient/parent feedback, resulting in estimates of 2.3-3.5 points for boys aged 7 to 10 years.
- Findings highlighted that patients and parents view a complete loss of function in one item or a decline in one to two items as significant changes, enhancing the understanding of clinical relevance in NSAA results.
Background: Acute flaccid paralysis (AFP) is characterized by rapidly progressive limb weakness with low muscle tone. It has a broad differential diagnosis, which includes acute flaccid myelitis (AFM), a rare polio-like condition that mainly affects young children. Differentiation between AFM and other causes of AFP may be difficult, particularly at onset of disease.
View Article and Find Full Text PDFAntisense oligonucleotide (ASO) mediated exon skipping aims to reframe dystrophin transcripts for patients with Duchenne muscular dystrophy (DMD). Currently 4 ASOs have been approved by the Food and Drug Administration targeting exon 45, 51 and 53 based on low level dystrophin restoration. Additional studies to confirm functional effects are ongoing.
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- Becker muscular dystrophy (BMD) shows slow progression, highlighting the need for biomarkers to support clinical trials; researchers examined changes in three muscle-enriched biomarkers in BMD patients over four years to evaluate their relation to disease severity and progression.
- The study involved measuring creatine kinase, creatine/creatinine levels, and myostatin in patient serum while assessing functional performance through various tests, revealing a strong correlation between Cr/Crn and myostatin with functional outcomes, but a weak association with creatine kinase.
- Outcomes from 34 patients indicated that specific biomarkers could explain up to 75% of the variance in functional performance, although dystrophin levels did not show a correlation with these biomarkers or patient performance
Article Synopsis
- The study aimed to evaluate the effectiveness and safety of givinostat, a treatment for Becker muscular dystrophy (BMD), in adult males, comparing it to a placebo over 12 months.
- Out of 51 enrolled patients, the treatment did not show a statistically significant improvement in total fibrosis or other primary endpoints after 12 months, although secondary MRI assessments hinted that givinostat might slow disease progression.
- Most adverse events reported were mild to moderate, with 88.2% of patients on givinostat and 52.9% on placebo experiencing side effects.
Article Synopsis
- Clinical trials for Duchenne muscular dystrophy (DMD) typically use genotype-matched controls, which complicates patient enrollment due to this rare disease's limited pool.
- The study analyzed over 1,600 patient-years from multiple sources to understand the impact of different genotype classes on motor function changes over a year.
- Results indicated that genotype only accounted for about 2% of variation in motor function outcomes, suggesting that utilizing unmatched controls in trials could be a viable option.
Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin, but many patients have rare revertant fibers that express dystrophin. The skeletal muscle pathology of DMD patients includes immune cell infiltration and inflammatory cascades. There are several strategies to restore dystrophin in skeletal muscles of patients, including exon skipping and gene therapy.
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- Acute flaccid myelitis (AFM) is a rare, polio-like condition mainly affecting children and linked to non-polio-enteroviruses like EV-D68 and EV-A71; this study specifically focused on AFM incidence in the Netherlands from 2014 to 2019.
- Out of 143 patients reviewed, only eight had definite AFM, leading to a low incidence rate of 0.06 cases per 100,000 children per year, with EV-D68 detected in five respiratory samples but no EV-A71 found.
- The findings indicate that while AFM is rare, its occurrence does seem to align with outbreaks of EV-D68, highlighting the need for better awareness and monitoring among healthcare
Muscle-specific kinase (MuSK) myasthenia gravis (MG) is a neuromuscular autoimmune disease belonging to a growing group of IgG4 autoimmune diseases (IgG4-AIDs), in which the majority of pathogenic autoantibodies are of the IgG4 subclass. The more prevalent form of MG with acetylcholine receptor (AChR) antibodies is caused by IgG1-3 autoantibodies. A dominant role for IgG4 in autoimmune disease is intriguing due to its anti-inflammatory characteristics.
View Article and Find Full Text PDFBackground: Overweight is a common problem in Duchenne muscular dystrophy (DMD) and is associated with reduced mobility and quality of life. The influence of nutritional intake on (over)weight is unclear.
Objective: To investigate weight and energy and macronutrients intake compared to age-specific requirements in DMD patients (4-18 years).
Article Synopsis
- Long-term use of corticosteroidal anti-inflammatory drugs can negatively impact patient quality of life, highlighting the need for safer alternatives.
- The study tested vamorolone, a new type of dissociative steroid, for its effectiveness and safety in boys aged 4 to under 7 with Duchenne muscular dystrophy (DMD) over a 24-week period.
- Results showed that vamorolone (6 mg/kg) significantly improved motor function compared to placebo, while the safety profile was potentially better than traditional corticosteroids.
Background: In Becker muscular dystrophy evidence for neurocognitive and behavioral comorbidity is evolving. More insight into the extend of these problems is of great importance for early detection and remediation in clinical practice.
Objective: In this study we aimed to describe the neurocognitive and behavioral features of a Dutch adult cohort of BMD patients, and to evaluate correlations to motor function outcomes.
Background: Outcome measures for non-ambulant Duchenne muscular dystrophy (DMD) patients are limited, with only the Performance of the Upper Limb (PUL) approved as endpoint for clinical trials.
Objective: We assessed four outcome measures based on devices developed for the gaming industry, aiming to overcome disadvantages of observer-dependency and motivation.
Methods: Twenty-two non-ambulant DMD patients (range 8.
Article Synopsis
- Using real-world data (RWD) and natural history data (NHD) for evaluating drugs in Duchenne muscular dystrophy (DMD) offers a solution to the difficulties of enrolling participants in placebo-controlled trials.
- A study compared the changes in the North Star Ambulatory Assessment (NSAA) scores between placebo trial arms and RWD/NHD data, revealing that the differences were minor before and after adjusting for baseline factors.
- The findings suggest that RWD/NHD external controls are appropriate for DMD drug evaluations, as they align with earlier results and provide a solid method for accounting for prognostic factors.
BMI-z scores of boys with Duchenne muscular dystrophy already begin to increase before losing ambulation: a longitudinal exploration of BMI, corticosteroids and caloric intake.
Neuromuscul Disord
March 2022
We aimed to investigate BMI-z course in patients with Duchenne muscular dystrophy (DMD) during transition to loss of ambulation, and to explore the contribution of caloric intake and corticosteroid use. A retrospective multicenter longitudinal study was conducted. First, analyses of characteristics at first visit were carried out.
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