Publications by authors named "Vivo D"
Article Synopsis
- At 12 months, apitegromab showed improved motor function and a favorable safety profile in patients with Type 2 or 3 spinal muscular atrophy (SMA); this study reports on the extended effects after 36 months for nonambulatory patients.
- In the open-label extension of the study, 35 nonambulatory patients received apitegromab and were evaluated using various assessments, resulting in significant improvements in motor scores and caregiver-reported outcomes over 36 months.
- The positive effects of apitegromab observed at 12 months were maintained at 36 months, with common side effects including fever, nasopharyngitis, and respiratory infections, but no new safety concerns were identified. *
Background And Objectives: Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020.
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- Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations in the survival motor neuron 1 gene, leading to progressive muscle degeneration, prompting a need to update diagnosis best practices post-treatment advancements and newborn screening implementation.
- A systematic review and expert consensus from healthcare professionals in the U.S. and Europe emphasized the critical role of newborn screening (NBS) for SMA and established new recommendations for characterizing NBS-identified infants and enhancing specialty care services.
- The working group highlighted the necessity of involving individuals with SMA and their caregivers in the process to better support and provide resources for those diagnosed through NBS, while noting limited data on adult-onset SMA diagnosis.
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by a varying degree of severity that correlates with the reduction of SMN protein levels. Motor neuron degeneration and skeletal muscle atrophy are hallmarks of SMA, but it is unknown whether other mechanisms contribute to the spectrum of clinical phenotypes. Here, through a combination of physiological and morphological studies in mouse models and SMA patients, we identify dysfunction and loss of proprioceptive sensory synapses as key signatures of SMA pathology.
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- The study investigates the effects of joint hypermobility (JH) on function in individuals with spinal muscular atrophy (SMA), highlighting the common occurrence of muscle weakness and contractures.
- A significant majority (86%) of participants exhibited at least one hypermobile joint, with specific correlations found between JH in hip extension and overall function scores, as well as between ankle plantar flexion and walking distance.
- The findings suggest that understanding the relationship between lower-limb range of motion and function is crucial for enhancing future rehabilitation approaches for those with SMA.
Background: Paroxysmal movement disorders are common in Glut1 deficiency syndrome (Glut1DS). Not all patients respond to or tolerate ketogenic diets.
Objectives: The objective was to evaluate the effectiveness and safety of triheptanoin in reducing the frequency of disabling movement disorders in patients with Glut1DS not receiving a ketogenic diet.
Background And Purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort.
Methods: The study employed two distinct methods.
Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by progressive motor function decline. Motor function is assessed using several functional outcome measures including the Revised Hammersmith Scale (RHS).
Objective: In this study, we present longitudinal trajectories for the RHS in an international cohort of 149 untreated paediatric SMA 2 and 3 patients (across 531 assessments collected between March 2015 and July 2019).
Article Synopsis
- Long-term real-world data on the effectiveness and safety of onasemnogene abeparvovec for spinal muscular atrophy (SMA) is crucial for understanding outcomes outside clinical trials.
- The RESTORE registry tracked 168 patients treated with this therapy, revealing a median age of 3 months at treatment and a majority identified through newborn screening.
- Results showed all patients maintained or achieved motor milestones, but nearly half experienced at least one adverse event, reinforcing the treatment's safety profile.
Article Synopsis
- The research aimed to create a structured method for classifying treatments aimed at modifying diseases related to survival motor neuron (SMA).
- The classification system categorizes treatments based on whether they are initial therapies or involve the continuation/discontinuation of further therapies, with specific treatment scenarios identified.
- By applying this classification to 443 patients in the RESTORE registry, the study examined patient demographics and established a framework for analyzing the safety and effectiveness of various treatment combinations in SMA.
Nusinersen has been shown to improve or stabilize motor function in individuals with spinal muscular atrophy (SMA). We evaluated baseline scoliosis severity and motor function in nusinersen-treated non-ambulatory children with later-onset SMA. Post hoc analyses were conducted on 95 children initiating nusinersen treatment in the CHERISH study or SHINE long-term extension trial.
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- The NURTURE study investigated the effects of nusinersen on children with spinal muscular atrophy (SMA) who started treatment before showing symptoms, finding positive outcomes in survival, motor milestones, and safety after 5 years.
- All participating children remained alive, with significant motor skill achievements, particularly among those with three SMN2 gene copies.
- Results emphasize the benefits of early treatment for SMA and the importance of considering specific criteria when evaluating trial data.
Background: Pharmacokinetic/pharmacodynamic modeling indicates that the higher dose of nusinersen may be associated with a clinically meaningful increase in efficacy above that seen with the 12-mg approved dose.
Objective: Here we describe both the design of DEVOTE (NCT04089566), a 3-part clinical study evaluating safety, tolerability, and efficacy of higher dose of nusinersen, and results from the initial Part A.
Methods: DEVOTE Part A evaluates safety and tolerability of a higher nusinersen dose; Part B assesses efficacy in a randomized, double-blind design; and Part C assesses safety and tolerability of participants transitioning from the 12-mg dose to higher doses.
Article Synopsis
- Fatigue and performance fatigability are significant issues in Spinal Muscular Atrophy (SMA) that negatively affect patients' quality of life and daily functioning.
- The review evaluates existing patient-reported fatigue scales used in SMA, analyzing their strengths and weaknesses.
- It suggests creating new patient-reported measures to better assess perceived fatigability, which could improve the evaluation of treatment effects.
Article Synopsis
- In utero exposure to maternal antibodies against fetal acetylcholine receptors can cause severe conditions like arthrogryposis multiplex congenita (AMC) and the milder fetal acetylcholine receptor inactivation syndrome (FARIS), but the full impact remains unclear.
- A study of 46 cases reveals that many affected mothers did not have prior diagnoses of myasthenia gravis, suggesting underreporting and missed preventative measures.
- Among the findings, significant long-term effects in surviving infants included various physical weaknesses, respiratory issues, and unexpected conditions like hearing loss; treatment with oral salbutamol showed promising improvement in symptoms for many children.
Background And Objective: GLUT1 deficiency syndrome (Glut1DS) is a treatable neurometabolic disease that causes a wide range of neurologic symptoms in children and adults. However, its diagnosis relies on an invasive test, that is, a lumbar puncture (LP) to measure glycorrhachia, and sometimes complex molecular analyses of the gene. This procedure limits the number of patients able to receive the standard of care.
View Article and Find Full Text PDFDefects in the light-evoked responses of the retina occur early in the sequalae of diabetic retinopathy (DR). These defects, identified through the electroretinogram (ERG), represent dysfunction of retinal neurons and the retinal pigment epithelium and are commonly identifiable at the timing of, or almost immediately following, diabetes diagnosis. Recently, systemic reduction of the facilitated glucose transporter type 1, Glut1, in type 1 diabetic mice was shown to reduce retinal sorbitol accumulation, mitigate ERG defects, and prevent retinal oxidative stress and inflammation.
View Article and Find Full Text PDFObjective: The goal of this study is to demonstrate the utility of a growth assay to quantify the functional impact of single nucleotide variants (SNVs) in SLC2A1, the gene responsible for Glut1DS.
Methods: The functional impact of 40 SNVs in SLC2A1 was quantitatively determined in HAP1 cells in which SLC2A1 is required for growth. Donor libraries were introduced into the endogenous SLC2A1 gene in HAP1-Lig4KO cells using CRISPR/Cas9.
Article Synopsis
- The Revised Hammersmith Scale (RHS) is a 36-item tool used to assess motor function in children with Spinal Muscular Atrophy (SMA), and this study focuses on changes in RHS scores over two years for different SMA types.
- A new transitional group of children, spanning various mobility levels, showed the most notable decline in scores, especially among those who can crawl, stand, and walk with assistance, highlighting the importance of this group's unique characteristics.
- The RHS demonstrates less floor effect compared to the Hammersmith Functional Motor Scale-Expanded (HFMSE) and is most effective when combined with the Revised Upper Limb Module (RULM) for participants with lower scores, while
Introduction/aims: Fatiguability and perceived fatigue are common unrelated symptoms in ambulatory individuals with spinal muscular atrophy (SMA). Ratings of perceived exertion (RPE) measures the sense of effort during an activity and has been used as a proxy for fatigue. Relationships between perceived fatigue, fatiguability, and RPE have been described in healthy populations, but the relationship in SMA has not been examined.
View Article and Find Full Text PDFObjective: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement.
Methods: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay.
Article Synopsis
- The study aims to explore the potential for a higher dose of nusinersen to improve clinical outcomes for infants with spinal muscular atrophy (SMA), by analyzing how CSF drug levels relate to biomarkers and clinical effects.
- Data from previous studies (CS3A and ENDEAR) showed that increased CSF levels of nusinersen are linked to significant decreases in a specific biomarker (pNF-H) and improved motor function scores (CHOP INTEND).
- Findings suggest that a higher dose could enhance treatment effectiveness, predicting a notable increase in CHOP INTEND scores, and further research is ongoing in the DEVOTE study to confirm safety and efficacy of this higher dosage.
Objective: To examine the correlation between verbal and visual memory function and correlation with brain metabolites (lactate and N-Acetylaspartate, NAA) in individuals with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).
Methods: Memory performance and brain metabolites (ventricular lactate, occipital lactate, and occipital NAA) were examined in 18 MELAS, 58 m.3243A > G carriers, and 20 familial controls.
Objective: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS).
Methods: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo.