NCALD Antisense Oligonucleotide Therapy in Addition to Nusinersen further Ameliorates Spinal Muscular Atrophy in Mice

Spinal muscular atrophy (SMA) is a neuromuscular disease causing the most frequent genetic childhood lethality. Recently, nusinersen, an antisense oligonucleotide (ASO) that corrects SMN2 splicing and thereby increases full-length SMN protein, has been approved by the FDA and EMA for SMA therapy. However, the administration of nusinersen in severe and/or post-symptomatic SMA-affected individuals is insufficient to counteract the disease. Therefore, additional SMN-independent therapies are needed to support the function of motoneurons and neuromuscular junctions.
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research

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Condition:   Muscular Atrophy, Spinal Intervention:   Drug: Nusinersen Sponsor:   Biogen Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of alpha motor neurons, clinically associated with muscle weakness, hypotonia and muscle atrophy. The weakness is predominant in the proximal muscles, with lower limbs often more involved than upper limbs with a typical distribution [1]. In the most severe cases the involvement is more diffuse affecting both proximal and distal muscles with very limited movements of hands and feet. The predominant proximal involvement has also been observed on muscle Magnetic Resonance Imaging (MRI) [2,3].
Source: Neuromuscular Disorders - Category: Neurology Authors: Tags: Picture of the month Source Type: research
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease associated with progressive and often severe muscle weakness and atrophy and is a leading cause of death in infants [1-4]. SMA is caused by homozygous deletions ( ∼95% of SMA patients) or compound heterozygous mutations (∼5% of SMA patients) in the survival motor neuron 1 (SMN1) gene that prevent production of full-length functional SMN protein.[5] The paralogous gene SMN2 undergoes aberrant splicing and produces mostly truncated, dysfunctional protein (∼ 90%) [1].
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
In this study we investigated the potential value of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in characterizing changes in the cervical spinal cord and peripheral nerve roots in vivo in patients with spinal muscular atrophy (SMA).MethodsWe developed an MRI protocol with 4 sequences to investigate the cervical spinal cord and nerve roots on a 3 Tesla MRI system. We used 2 anatomical MRI sequences to investigate cross-sectional area (CSA) at each spinal segment and the diameter of ventral and dorsal nerve roots, and two diffusion tensor imaging (DTI) techniques to estimate the fractional anisotropy...
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
Nature Reviews Neurology, Published online: 04 September 2019; doi:10.1038/s41582-019-0262-5Alternative gene therapy target identified in spinal muscular atrophy mice
Source: Nature Reviews Neurology - Category: Neurology Authors: Source Type: research
The objective of this study was to create and test gene-editing systems for correction of the single-nucleotide substitution c.840C>T in exon 7 of theSMN2 gene in fibroblasts, induced pluripotent stem cells, and motor neuron progenitors derived from a SMA patient. For this purpose, we used plasmid vectors expressing CRISPR/Cas9 and CRISPR/Cpf1, plasmid donor, and 90-nt single-stranded oligonucleotide templates that were delivered to the target cells by electroporation. Although sgRNA_T2 and sgRNA_T3 guiding RNAs were more efficient than sgRNA_T1 in fibroblasts (p
Source: Biochemistry (Moscow) - Category: Biochemistry Source Type: research
Multivitamins, drugs, gene therapies, human skin, heart, eyeballs, kidneys, entire dead bodies – everything comes with a price tag. Putting aside the moral questions of why and how come that the capitalist market priced even our body parts and health, we asked the question of how much is life worth: what is the maximum that you would/should pay for a life-saving drug? How high is too high a cost if a drug can save 200-300 babies a year from debilitating illness or death? And ultimately, does the pricing of new technologies, especially gene therapies, enable to fulfill their promise? There’s a price for ever...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Bioethics Biotechnology Future of Pharma Genomics cost daraprim drug drug price Gene gene therapy genetics insulin life medication pricing policy rare disease rare disorder Source Type: blogs
Purpose of review To review the advent of novel therapies and their impact on the field of chromosome 5q-associated spinal muscular atrophy (SMA). Recent findings Antisense oligonucleotides (ASOs) enhancing SMN2 function are delivered intrathecally and small molecules will also be available soon delivered by the oral route; alternatively, systemic injection of viral vectors in order to replace the SMN gene are likely to be available in the future. In summer 2019, it remains the core finding that intrathecally delivered ASOs convincingly change the natural history of the disease in children and that the treatment effec...
Source: Current Opinion in Neurology - Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert C. Ludolph Source Type: research
We report the development of a new disease registry on SMA as the result of a collaboration among three national networks in United States, Italy, and United Kingdom in partnership with a biotechnology company and with the support of advocacy groups.The aim of establishing a large collaborative registry within academic centers was to establish a structured but flexible system for collection of prospective, highly curated data that will deeply phenotype all patients with SMA and follow them longitudinally over several years.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Abstract In April 2019, a ruling was signed for the incorporation of the drug nusinersen by the Brazilian Unified National Health System (SUS). Nusinersen is the most expensive drug ever incorporated by the SUS and is used to treat type I 5q spinal muscular atrophy. The incorporation has been described as a milestone in decision-making on new technologies in the SUS, enabled through a risk-sharing agreement. The article discusses the process involved in the incorporation of nusinersen, highlighting the context, timing, and technical issues, in addition to possible consequences for the institutionalization of healt...
Source: Cadernos de Saude Publica - Category: International Medicine & Public Health Authors: Tags: Cad Saude Publica Source Type: research
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