Identification of Biochemical Determinants for Diagnosis and Prediction of Severity in 5q Spinal Muscular Atrophy Using H-Nuclear Magnetic Resonance Metabolic Profiling in Patient-Derived Biofluids.

This study explores the potential of H-NMR spectroscopy-based metabolic profiling in various biofluids as a diagnostic and predictive modality to assess disease severity in individuals with 5q spinal muscular atrophy. A total of 213 biosamples (urine, plasma, and CSF) from 153 treatment-naïve patients with SMA across five German centers were analyzed using H-NMR spectroscopy. Prediction models were developed using machine learning algorithms which enabled the patients with SMA to be grouped according to disease severity.

The Relevance of Spinal Muscular Atrophy Biomarkers in the Treatment Era.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that currently has an approved treatment for all forms of the disease. Previously, biomarkers were primarily used for diagnostic purposes, such as detecting the presence of the disease or determining a specific clinical type of SMA. Currently, with the availability of therapy, biomarkers have become more valuable due to their potential for prognostic, predictive, and pharmacodynamic applications.

MicroRNAs as Biomarkers in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic cause, gene-targeted therapies have been developed, aiming to increase SMN production in SMA patients. The SMN protein is likely involved in the synthesis of microRNAs (miRNAs), and dysregulated miRNA expression is increasingly associated with the pathophysiology of SMA.

Neuromuscular diseases: genomics-driven advances.

Neuromuscular diseases (NMDs) are a group of rare disorders characterized by significant genetic and clinical complexity. Advances in genomics have revolutionized both the diagnosis and treatment of NMDs. While fewer than 30 NMDs had known genetic causes before the 1990s, more than 600 have now been identified, largely due to the adoption of next-generation sequencing (NGS) technologies such as whole-exome sequencing (WES) and whole-genome sequencing (WGS).

Functional Outcome Measures to Optimize Drug Development in Spinal and Bulbar Muscular Atrophy: Results From a Meta-Analysis of the Global SBMA Dataset.

Background And Objectives: Spinal and bulbar muscular atrophy (SBMA) is a rare, slowly progressive, and debilitating disease without effective treatments available. Lack of reliable biomarkers and sensitive outcome measures makes clinical research conduct challenging. The primary objective of this study was to identify clinically meaningful and statistically sensitive outcome measures enabling the evaluation of therapeutic interventions in late-stage clinical trials.

A Case Series Examining Clinic, Laboratory, and Physical Function After Administration of Nusinersen in Adults With Spinal Muscular Atrophy, a Single-Center Study.

Spinal muscular atrophy is an incurable inherited disease caused by lower motor neuron death from mutations of the survival motor neuron genes. Intrathecal therapy with the antisense oligonucleotide, nusinersen, has been demonstrated to be beneficial in children with this disease, but the experience in adults, particularly ambulatory patients, is limited. We present a prospective observational case series from a single center using nusinersen therapy where we categorize 6 adult patients with spinal muscular atrophy into 2 functional categories: ambulatory (n = 3) or nonambulatory (n = 3).

Concomitant telomere attrition is associated with spinal muscular atrophy in highly inbred region of North India: unraveling the thread in Kashmir region.

Spinal muscular atrophy (SMA) is a rare genetic disorder that unequivocally results in the degeneration of motor neurons, leading to muscle weakness and atrophy. This condition is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which inevitably results in a deficiency of the SMN protein. In present study, we investigated the potential role of telomere attrition in SMA patients.

Efficacy of Nusinersen Treatment in Type 1, 2, and 3 Spinal Muscular Atrophy: Real-World Data from a Single-Center Study.

Background: Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive muscle weakness and atrophy due to the absence of the survival motor neuron 1 () gene. SMA is classified into types 0 through 4 based on the age of symptom onset and the severity of motor function decline. Recent advances in SMA treatment, including nusinersen, onasemnogene abeparvovec, and risdiplam, have significantly improved the prognosis of SMA patients.

Development and validation of a one-step assay for genetic testing in spinal muscular atrophy MALDI-TOF MS.

Spinal muscular atrophy (SMA) is a fatal neuromuscular disorder primarily attributed to the homozygous deletion of the survival motor neuron 1 () gene, with disease severity closely correlated to the copy number variations (CNV) of . Conventional methodologies, however, fail to provide a comprehensive gene overview of and are often both time-intensive and costly. In this study, we present a novel one-step MALDI-TOF MS assay for SMA gene testing.

[Use of disease-modifying therapies in spinal muscular atrophy 5q in Mexico].

5q Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease that causes weakness in the limbs, trunk, diaphragm, and bulbar muscles; without treatment it can lead to severe motor disability and even death. The Food and Drug administration (FDA) and COFEPRIS (Mexico's Federal Committee for Protection against Sanitary Risks) have approved 3 therapies to increase the production of survival motor neuron (SMN) protein and improve muscle strength and quality of life in patients: nusinersen, onasemnogene abeparvovec xioi, and risdiplam. Despite the fact that these therapies have shown efficacy, at the moment it is not possible to establish which of them is superior compared to the others.

Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3.

Background And Objective: Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities and cognitive impairment have been reported in severe SMA.

Risdiplam: therapeutic effects and tolerability in a small cohort of 6 adult type 2 and type 3 SMA patients.

Background: Risdiplam is a validated treatment for adult SMA patients, but clear guidelines concerning functional assessment at baseline and during the follow-up are still limited, especially in terms of sensible and validated outcome measures able to capture minimal changes in motor performances induced by therapy. The aim of this work is to describe the effect of Risdiplam on a cohort of 6 adult type 2 and type 3 SMA patients, using Motor Function Measure (MFM32) as a standardized scaleto quantify the motor improvements induced by therapy.

Results: Risdiplam at the dose of 5 mg/daily was administered to a population of 6 (4 F;2 M) type 2 (N = 4) and type 3 (N = 2), adult SMA patients.

Gratitude Experience in Ten Patients with Spinal Muscular Atrophy: A Qualitative Study.

Objective: This study aimed to investigate the gratitude experience of young and middle-aged patients with spinal muscular atrophy (SMA) during hospitalisation to provide a theoretical basis for medical professionals to develop gratitude intervention programs.

Methods: Patients with SMA who were treated with nusinersen in the Department of Neurology of the First Hospital of Jilin University between April 20 and May 20, 2024 were selected using the purposive sampling method, and semi-structured interviews were conducted. The interview data were analysed using Colaizzi's 7-step analysis method.

Managing the challenges of paying for gene therapy: strategies for market action and policy reform in the United States.

Gene therapies delivered through a single administration have revolutionized treatment possibilities for many patients living with serious or fatal conditions such as spinal muscular atrophy, hemophilia and sickle cell disease. However, shadowing the excitement about the transformational potential of many gene therapies has been widespread concern about the combination of uncertainty in the durability of their benefits over the long term and the short-term financial shock of high prices. As the healthcare payment ecosystem prepares for the growing number of gene therapies entering the market, three key interconnected challenges must be addressed: determining a fair price, managing clinical uncertainty and managing short-term budget impacts.

The impact of neurological impairment and tone on hip joint development.

Purpose: The purpose of this study was to define how different force environments by neuromuscular diagnosis (hypertonic versus hypotonic) impact the growth and morphology of the proximal femoral and acetabular regions relative to typically developing children.

Methods: Children with cerebral palsy and spinal muscular atrophy were compared with typically developing children aged 6 months to 11 years. Routine pelvic radiographs were evaluated using measures of hip geometry for the proximal femur and acetabulum.