scholarly journals New Therapeutics Options for Pediatric Neuromuscular Disorders

2020 ◽  
Vol 8 ◽  
Author(s):  
Marina Flotats-Bastardas ◽  
Andreas Hahn
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Atrophy ◽  
Neuromuscular Disorders ◽  
Genetic Defect ◽  
New Drugs ◽  
Anterior Horn Cell ◽  
Childhood Onset ◽  
Course Of Disease ◽  
New Therapies ◽  
Prolonged Life Expectancy

Neuromuscular disorders (NMDs) of Childhood onset are a genetically heterogeneous group of diseases affecting the anterior horn cell, the peripheral nerve, the neuromuscular junction, or the muscle. For many decades, treatment of NMDs has been exclusively symptomatic. But this has changed fundamentally in recent years due to the development of new drugs attempting either to ameliorate secondary pathophysiologic consequences or to modify the underlying genetic defect itself. While the effects on the course of disease are still modest in some NMDs (e.g., Duchenne muscular dystrophy), new therapies have substantially prolonged life expectancy and improved motor function in others (e.g., spinal muscular atrophy and infantile onset Pompe disease). This review summarizes recently approved medicaments and provides an outlook for new therapies that are on the horizon in this field.

Respiratory load compensation in neuromuscular disorders

1988 ◽  
Vol 64 (6) ◽  
pp. 2659-2666 ◽  
Author(s):  
K. Axen ◽  
M. Bishop ◽  
F. Haas
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Atrophy ◽  
Neuromuscular Disorders ◽  
Neural Mechanisms ◽  
Load Compensation ◽  
Ventilatory Responses ◽  
Duty Cycles ◽  
Human Ability ◽  
Loaded Breathing ◽  
Muscle Disorder

First-breath ventilatory responses to graded elastic (delta E) and resistive (delta R) loads from 10 people with spinal muscular atrophy (SMA), 15 people with Duchenne muscular dystrophy (DMD), and 80 able-bodied people were compared. The SMA and DMD groups produced equal tidal volume, respiratory frequency, inspiratory duration (TI), expiratory duration, mean inspiratory airflow, and duty cycle responses to both delta E and delta R. Thus SMA (primarily a motoneuron disorder) and DMD (primarily a muscle disorder) have the same net effect on loaded breathing responses. The SMA and DMD groups failed to duplicate the normal group's short expirations during delta E, long inspirations during delta R, and thus, extended duty cycles during both delta E and delta R. The deficit in load compensation therefore was due to impaired regulation of respiratory timing (reflecting neural mechanisms) but not airflow defense (reflecting mechanical and neural mechanisms). One-fifth of the normal but none of the SMA or DMD subjects actively generated an "optimal" TI response (defined theoretically as TI greater than 160% control during large delta R and TI less than 75% control during large delta E). This lack of optimal responses, which is the same abnormality exhibited by quadriplegic people, suggests that SMA and DMD also impair human ability to discriminate between large delta R and delta E. These findings support the hypothesis that neuromuscular disorders can lead to disturbances in respiratory perception.

scholarly journals Feasibility and effectiveness of a novel dynamic arm support in persons with spinal muscular atrophy and duchenne muscular dystrophy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mariska M. H. P. Janssen ◽  
Jolinda Horstik ◽  
Paulien Klap ◽  
Imelda J. M. de Groot
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Spinal Muscular Atrophy ◽  
Range Of Motion ◽  
Upper Extremity ◽  
Muscular Atrophy ◽  
Neuromuscular Disorders ◽  
Median Increase ◽  
Active Range Of Motion ◽  
Arm Support

Abstract Background Neuromuscular disorders (NMD) commonly affect the upper extremity. Due to muscle weakness, performance of daily activities becomes increasingly difficult, which leads to reduced independence and quality of life. In order to support the performance of upper extremity tasks, dynamic arm supports may be used. The Yumen Arm is a novel dynamic arm support specially developed for people with NMD. The aim of this study is to evaluate the feasibility and effectiveness of the Yumen Arm in persons with Duchenne Muscular Dystrophy (DMD) and persons with Spinal Muscular Atrophy (SMA). Methods Three persons with DMD and three persons with SMA participated in this study. All participants conducted a set of measures with and without the Yumen Arm. Outcome measures were: active range of motion of the arm and trunk (i.e. Reachable Workspace, Functional Workspace, and trunk movement), fatigue (OMNI-RPE), Performance of Upper Limb (PUL) scale and some additional activities of daily living. User experiences were collected using a questionnaire. Results The Yumen Arm could be used by all participants. Results showed a median increase in active range of motion (4% relative surface area), and a median increase of function ability (> 11% PUL score) when using the Yumen Arm. In addition, three out of four (data from 2 participants was missing) participants indicated that activity performance was less fatiguing when using the Yumen Arm. Four out of five (data from 1 participant was missing) participants indicated that they would like to use the Yumen Arm in their daily lives. Conclusion This study is one of the first studies describing a range of objective measures to examine the effectiveness of a dynamic arm support. Based on these measurements we can conclude that the Yumen Arm effectively improves arm function in NMD patients, however the effectiveness varies a lot between individual subjects. We provided detailed recommendations for the improvement of the Yumen Arm, and possible also for the development of other dynamic arm supports. This study showed a lot of variability between individual subjects, which emphasizes the importance of tuning dynamic arm supports based on individual user characteristics, such as scoliosis, functional capacity and muscle strength.

scholarly journals Importance and Benefits of Patient Registries for Duchenne Muscular Dystrophy

2015 ◽  
Vol 10 (01) ◽  
pp. 79
Author(s):  
Olivia Schreiber-Katz ◽  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Patient Care ◽  
Rare Diseases ◽  
Public Awareness ◽  
Childhood Onset ◽  
Patient Registries ◽  
New Therapies ◽  
Special Challenge ◽  
Data Harmonisation

Rare diseases represent a special challenge for the translation of new therapies into patient care. Duchenne muscular dystrophy (DMD) is a rare childhood-onset muscular dystrophy; curative treatment is not yet available. However, new therapies are emerging to fight this devastating disease. In order to establish an infrastructure to improve data harmonisation, knowledge on the disease, public awareness, industrial interest and trial readiness, patient registries are an indispensable resource. This article provides a short overview on their importance and benefits towards improving diagnosis and care.

scholarly journals Spinal muscular atrophy (5qSMA): best practice of diagnostics, newborn screening and therapy

2020 ◽  
Vol 32 (3) ◽  
pp. 263-272
Author(s):  
Katja Eggermann ◽  
Dieter Gläser ◽  
Angela Abicht ◽  
Brunhilde Wirth
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
Best Practice ◽  
Muscular Atrophy ◽  
Neuromuscular Disorders ◽  
Genetic Defect ◽  
Homozygous Deletion ◽  
Survival Motor Neuron ◽  
Compound Heterozygous ◽  
Common Mutation

Abstract Proximal spinal muscular atrophy (SMA) is an autosomal-recessive inherited neuromuscular disorder caused by the degeneration of alpha motor neurons in the anterior horn of the spinal cord. Patients show hypotonia, muscular atrophy and weakness of voluntary proximal muscles. SMA is one of the most common genetic diseases, with a frequency of about 1 in 7,000 newborns in Germany. The vast majority of patients carry a homozygous deletion of exons 7 and 8 of the survival motor neuron (SMN) 1 gene on chromosome 5q13.2; only about 3–4 % of patients are compound heterozygous for this common mutation and an additional subtle mutation in SMN1. The severity of the disease is mainly influenced by the copy number of the highly homologous SMN2. Since the discovery of the underlying genetic defect 25 years ago, both the diagnostics of SMA and its treatment have undergone constant and in recent times rapid improvements. SMA has become one of the first neuromuscular disorders with effective therapies based on gene targeted strategies such as splice correction of SMN2 via antisense oligonucleotides or small molecules or gene replacement therapy with a self-complementary adeno-associated virus 9 expressing the SMN1-cDNA. With the availability of treatment options, which are most effective when therapy starts at a pre-symptomatic stage, a newborn screening is indispensable and about to be introduced in Germany. New challenges for diagnostic labs as well as for genetic counsellors are inevitable. This article aims at summarising the current state of SMA diagnostics, treatment and perspectives for this disorder and offering best practice testing guidelines to diagnostic labs.

Novel Drugs and Biologics of 2016: A Boom for Neurodrugs in the Pipelin

2017 ◽  
Vol 10 (5) ◽  
pp. 3809-3814
Author(s):  
D Samba Reddy
Keyword(s):  
Muscular Atrophy ◽  
Clinical Care ◽  
New Drugs ◽  
Essential Medicines ◽  
High Demand ◽  
The Past ◽  
Novel Drugs ◽  
Innovative Products ◽  
Cns Drugs ◽  
The U.S

This article provides a brief overview of novel drugs approved by the U.S. FDA in 2016.  It also focuses on the emerging boom in the development of neurodrugs for central nervous system (CNS) disorders. These new drugs are innovative products that often help advance clinical care worldwide, and in 2016, twenty-two such drugs were approved by the FDA. The list includes the first new drug for disorders such as spinal muscular atrophy, Duchenne muscular dystrophy or hallucinations and delusions of Parkinson’s disease, among several others. Notably, nine of twenty-two (40%) were novel CNS drugs, indicating the industry shifting to neurodrugs. Neurodrugs are the top selling pharmaceuticals worldwide, especially in America and Europe. Therapeutic neurodrugs have proven their significance many times in the past few decades, and the CNS drug portfolio represents some of the most valuable agents in the current pipeline. Many neuroproducts are vital or essential medicines in the current therapeutic armamentarium, including dozens of “blockbuster drugs” (drugs with $1 billion sales potential).  These drugs include antidepressants, antimigraine medications, and anti-epilepsy medications. The rise in neurodrugs’ sales is predominantly due to increased diagnoses of CNS conditions. The boom for neuromedicines is evident from the recent rise in investment, production, and introduction of new CNS drugs.  There are many promising neurodrugs still in the pipeline, which are developed based on the validated “mechanism-based” strategy. Overall, disease-modifying neurodrugs that can prevent or cure serious diseases, such as multiple sclerosis, epilepsy, and Alzheimer’s disease, are in high demand. 

scholarly journals MiRNAs and Muscle Regeneration: Therapeutic Targets in Duchenne Muscular Dystrophy

2021 ◽  
Vol 22 (8) ◽  
pp. 4236
Author(s):  
Amelia Eva Aránega ◽  
Estefanía Lozano-Velasco ◽  
Lara Rodriguez-Outeiriño ◽  
Felicitas Ramírez de Acuña ◽  
Diego Franco ◽  
...  
Keyword(s):  
Stem Cell ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Regeneration ◽  
Transcriptional Control ◽  
Neuromuscular Disorders ◽  
Critical Role ◽  
Gene Replacement ◽  
Control Of Gene Expression ◽  
Muscle Disorders

microRNAs (miRNAs) are small non-coding RNAs required for the post-transcriptional control of gene expression. MicroRNAs play a critical role in modulating muscle regeneration and stem cell behavior. Muscle regeneration is affected in muscular dystrophies, and a critical point for the development of effective strategies for treating muscle disorders is optimizing approaches to target muscle stem cells in order to increase the ability to regenerate lost tissue. Within this framework, miRNAs are emerging as implicated in muscle stem cell response in neuromuscular disorders and new methodologies to regulate the expression of key microRNAs are coming up. In this review, we summarize recent advances highlighting the potential of miRNAs to be used in conjunction with gene replacement therapies, in order to improve muscle regeneration in the context of Duchenne Muscular Dystrophy (DMD).

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