Publications by authors named "MOnica Povedano"
This is the first study aimed to detect morphological abnormalities in vivo in the skin capillaries of amyotrophic lateral sclerosis patients (ALS). Videocapillaroscopy assessed subungueal capillaries in 28 ALS patients (cases) and 35 controls (p = 0.42).
View Article and Find Full Text PDFThis study aimed to assess differences in the enteral microbiome of relatively recent-onset amyotrophic lateral sclerosis (ALS) patients (< 6-15 months since symptom onset) compared to healthy individuals, focusing on short-chain fatty acids (SCFAs) as potential mediators of host metabolism. We included 28 volunteers (16 ALS, 12 controls) with informed consent. No significant effect of ALS on alpha diversity (measuring the variety and abundance of species within a single sample, and indicating the health and complexity of the microbiome) was observed, but ALS patients had higher abundances of Fusobacteria and Acidobacteria.
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- - Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with about a three-year average survival time, primarily characterized by TDP-43 protein issues that affect gene stability and autophagy processes.
- - Research on ALS mice revealed that reducing ATG4B worsens survival and autophagy, while an increase in LC3ylation was observed in both ALS patients and mouse models, suggesting a link between these processes.
- - Antisense oligonucleotides (ASOs) targeting TDP-43 genes have been developed, showing potential for non-invasive treatments that can effectively distribute in the brain after administration.
A scoping review of the role of managed entry agreements in upcoming drugs for amyotrophic lateral sclerosis: learning from the case of spinal muscular atrophy.
Amyotroph Lateral Scler Frontotemporal Degener
February 2025
Article Synopsis
- * A scoping review was conducted across multiple databases, yielding a total of 45 initial results, narrowed down to six relevant studies discussing MEAs in SMA from different health organizations.
- * MEAs aim to alleviate financial and clinical uncertainties associated with costly medications, suggesting that existing MEA frameworks for SMA could inform similar strategies for ALS, given their common challenges.
Amyotrophic lateral sclerosis is a debilitating and lethal neurodegenerative disorder marked by the gradual deterioration of motor neurons. Diagnosing amyotrophic lateral sclerosis is challenging due to the lack of reliable diagnostic tools, with clinical assessment being the primary criterion. Recently, increased levels of neurofilament light chain in CSF have been considered a useful biomarker in disease, correlating with disease progression but not specific for diagnosis.
View Article and Find Full Text PDFThe objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months.
View Article and Find Full Text PDFGeographical distribution of clinical trials in amyotrophic lateral sclerosis: a scoping review.
Amyotroph Lateral Scler Frontotemporal Degener
May 2024
: Clinical trials location is determined by many factors, including the availability of patient populations, regulatory environment, scientific expertise, and cost considerations. In clinical drug development of amyotrophic lateral sclerosis (ALS), where genetic differences have been described and may be related to geographic setting, this could have implications for the clinical interpretation of results in underrepresented geographic settings. : The aim of this study was to review country participation in ALS clinical research based on available data from clinical trial registries and databases.
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- Amyotrophic lateral sclerosis (ALS) is a serious motor neuron disease that can also exhibit cognitive and behavioral symptoms, often overlapping with frontotemporal dementia (FTD) in some patients.
- * Around 50% of patients with motor neuron disease experience cognitive issues, with 10-15% meeting the criteria for FTD, emphasizing the need for better diagnostic tools.
- * A study analyzed data from 124 MND patients to understand the prevalence of FTD-related changes and identified specific clinical, genetic, and pathological subgroup characteristics, finding that 35.5% had features of frontotemporal lobar degeneration (FTLD).
Introduction: The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation.
Methods: This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16 years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients' association (FundAME), participated in the design of the clinical tool.
LAENALS: epidemiological and clinical features of amyotrophic lateral sclerosis in Latin America.
Amyotroph Lateral Scler Frontotemporal Degener
February 2024
Article Synopsis
- The Latin American Epidemiologic study of ALS (LAENALS) focuses on understanding ALS by analyzing demographic data from Cuba, Chile, and Uruguay, particularly the genetic and environmental factors influencing the disease.
- Data was collected using a standardized protocol in each country between 2017 and 2019, with statistical analysis revealing varied incidence and prevalence rates across the three locations.
- Findings indicate that ALS incidence and prevalence are lower in populations with greater genetic diversity, and the LAENALS database is now available for further research in other Latin American countries.
Epidemiological and clinical profile of amyotrophic lateral sclerosis in Ethiopia: a 5-year multicenter retrospective study.
Amyotroph Lateral Scler Frontotemporal Degener
July 2023
Article Synopsis
- Amyotrophic lateral sclerosis (ALS) is a serious disease causing muscle weakness, with limited research on its impact in low- and middle-income countries like Ethiopia.
- A study in Ethiopia analyzed clinical records from 2016 to 2021, revealing a younger average age of onset at 51.9 years and a higher prevalence of spinal region involvement at diagnosis.
- Findings indicated that 31% of patients used the medication Riluzole, while many experienced significant disabilities, highlighting the need for further research to explore the genetic and environmental factors influencing ALS in this region.
Article Synopsis
- - This study investigates whether starting Non-Invasive Ventilation (NIV) earlier at an FVC of 75% improves outcomes in ALS patients compared to the standard initiation at 50%.
- - Conducted as a randomized clinical trial with 42 participants, results indicated a trend toward better survival and reduced respiratory decline in the early NIV group, although the findings weren't statistically significant.
- - The trial ultimately suggests that early NIV is tolerated well and may help slow respiratory muscle deterioration, supporting the need for earlier respiratory evaluations in ALS patients.
Article Synopsis
- The study investigates the (phospho)proteomic profile of older adults without cognitive issues or signs of Alzheimer's disease, aiming to better understand the physiological aspects of brain aging.
- Using label-free- and SWATH-MS techniques, the research analyzes the frontal cortex of individuals across four age groups, ranging from young adults (30-44 years) to late-elderly (75-85 years).
- Results indicate that while many protein levels remain stable until age 70, significant changes in proteins associated with cell membranes, synapses, and other cellular structures occur after age 75, suggesting a shift in brain biology that may precede neurological deficits.
Article Synopsis
- The text discusses the increasing gene testing for amyotrophic lateral sclerosis (ALS), particularly for sporadic ALS (sALS), highlighting a lack of large studies on genetic variations associated with the disease.
- It describes a research study that analyzed genetic data from over 6,000 sALS patients and over 2,400 controls to characterize genetic variability in 90 ALS-related genes using established criteria for interpretation.
- The findings revealed that while some pathogenic variants were identified, a significant portion of the sALS patients had no detectable genetic clues, indicating the complexity of the genetic landscape of the disease.*
Clinical and demographical characteristics in a cohort of MND patients treated with riluzole. Differences between tablets and oral suspension.
Amyotroph Lateral Scler Frontotemporal Degener
August 2023
Article Synopsis
- The study compares clinical and demographic traits of patients with Motor Neuron Disease (MND) treated with riluzole in two forms: oral suspension and tablets.
- A total of 742 patients were analyzed, revealing that the majority preferred tablet form, particularly among younger males and those without dysphagia, while older patients with dysphagia favored the oral suspension.
- Patients using oral suspension experienced poorer survival rates compared to those using tablets, highlighting the need for personalized dosage forms based on individual symptoms throughout the disease progression.
Voiceprint and machine learning models for early detection of bulbar dysfunction in ALS.
Comput Methods Programs Biomed
February 2023
Background And Objective: Bulbar dysfunction is a term used in amyotrophic lateral sclerosis (ALS). It refers to motor neuron disability in the corticobulbar area of the brainstem which leads to a dysfunction of speech and swallowing. One of the earliest symptoms of bulbar dysfunction is voice deterioration characterized by grossly defective articulation, extremely slow laborious speech, marked hypernasality and severe harshness.
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- * Data was collected from 17 centers, revealing 29 mutations in 144 patients, with the most common being p.Gly38Arg, and showing significant regional variations and the presence of novel mutations.
- * Older age at onset and female sex were linked to faster progression and shorter survival, indicating the need for targeted treatment approaches for SOD1 mutations in ALS.
Background: Given the large genetic heterogeneity in amyotrophic lateral sclerosis (ALS), it seems likely that genetic subgroups may benefit differently from treatment. An exploratory meta-analysis identified that patients homozygous for the C-allele at SNP rs12608932, a single nucleotide polymorphism in the gene UNC13A, had a statistically significant survival benefit when treated with lithium carbonate. We aim to confirm the efficacy of lithium carbonate on the time to death or respiratory insufficiency in patients with ALS homozygous for the C-allele at SNP rs12608932 in UNC13A.
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- Traditional outcome measures for spinal muscular atrophy (SMA) clinical trials are insufficient for capturing the complete severity of the disease, prompting a study to evaluate the psychometric properties of various questionnaires addressing patient and caregiver insights.
- Conducted as a multicenter, prospective, noninterventional study, it included 113 SMA patients aged 2 to 17 years and utilized a range of assessments, including existing scales and newly developed items to evaluate domains such as fatigue and vulnerability.
- The results demonstrated high reliability and construct validity for most measured domains, with perceived fatigability being notably affected and the SMA Independence Scale (SMAIS) showing sensitivity to changes, highlighting the need for improved assessment tools in SMA.
Article Synopsis
- ALS shows varying characteristics in how it starts and progresses.
- In a study of 246 ALS patients, higher levels of cerebrospinal fluid (CSF) proteins and albumin were linked to an increased risk of death, particularly in those with spinal ALS.
- Key thresholds identified were CSF proteins ≥ 0.5 g/L and albumin quotient (QAlb) ≥ 0.65, both indicating worse prognoses for patients.
Background And Purpose: Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients.
Methods: Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included.
Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype−phenotype correlation is not absolute.
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- The study investigates senescence mechanisms in the hSOD1-G93A motor neuron disease model by measuring markers like p16, p21, and SA-β-gal in nervous tissue.
- Researchers found elevated p16 and p21 levels in glial cells but no expected increase in SA-β-gal activity, suggesting a unique senescence profile.
- Additionally, they noted changes in SASP-related mRNA levels and TDP-43 splicing activity, while certain drugs had varied effects on these senescence markers and disease progression.
Article Synopsis
- The study aimed to evaluate the safety and effectiveness of nusinersen in adult patients with 5q spinal muscular atrophy (SMA), involving a cohort of patients over 15 years old who were followed for at least 6 months.
- Results showed that treated patients had significant improvements in motor function and overall health assessments compared to untreated patients, particularly noting a 2-point improvement in the Revised Upper Limb Module (RULM) score after 6 months.
- Despite most treated patients experiencing some adverse effects, primarily mild, the findings suggest that nusinersen could provide functional benefits, particularly for those on treatment for longer periods, although severely affected patients may face a less favorable risk-benefit outcome.