Genetic therapies for inherited neuromuscular disorders.

@article{Scoto2018GeneticTF,
  title={Genetic therapies for inherited neuromuscular disorders.},
  author={Mariacristina Scoto and Richard S. Finkel and Eugenio Mercuri and Francesco Muntoni},
  journal={The Lancet. Child \& adolescent health},
  year={2018},
  volume={2 8},
  pages={
          600-609
        }
}
Inherited neuromuscular disorders encompass a broad group of genetic conditions, and the discovery of these underlying genes has expanded greatly in the past three decades. The discovery of such genes has enabled more precise diagnosis of these disorders and the development of specific therapeutic approaches that target the genetic basis and pathophysiological pathways. Such translational research has led to the approval of two genetic therapies by the US Food and Drug Administration… 
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References

SHOWING 1-10 OF 75 REFERENCES
Progress toward Gene Therapy for Duchenne Muscular Dystrophy.
TLDR
Progress in the development of DMD gene therapy has been well documented in Molecular Therapy over the past 20 years and will be reviewed here to highlight prospects for success in the imminent human clinical trials planned by several groups.
Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease
TLDR
The chemical properties and molecular mechanisms of action of the antisense oligonucleotides and the therapeutic implications these compounds have in neuromuscular diseases are described.
Gene therapy for Duchenne muscular dystrophy
TLDR
An overview of the potential for gene therapy of DMD using AAV vectors including a summary of promising developments and issues that need to be resolved prior to large-scale therapeutic implementation is provided.
Childhood spinal muscular atrophy: controversies and challenges
TLDR
The development of standards of care for children with the disorder and the identification of promising treatment strategies have changed the natural history of spinal muscular atrophy, and the prospects are good for further improvements in function, quality of life, and survival.
Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q1 1.2–13.3
TLDR
Analysis of 13 clinically heterogeneous SMA families finds that 'chronic' childhood-onset SMA (including intermediate SMA or SMA type II, and Kugelberg–Welander or S MA type III) is genetically homogeneous, mapping to chromosomal region 5ql 1.3.
Development of Exon Skipping Therapies for Duchenne Muscular Dystrophy: A Critical Review and a Perspective on the Outstanding Issues
TLDR
A perspective on questions regarding the development and regulatory approval of AONs for DMD is presented following a European stakeholder meeting involving academics, regulators, and representatives from industry and patient organizations, and in the light of the most recent scientific and regulatory experience.
Newborn and carrier screening for spinal muscular atrophy
TLDR
It is demonstrated that an effective technology does exist for newborn screening of SMA and an estimate of the carrier frequency among individuals who accepted carrier screening is provided, to report on patient's knowledge and attitudes toward SMA testing.
Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy.
TLDR
The authors summarize the mechanistic principles behind various antisense targets currently available for SMA therapy, including intronic splicing silencer N1 (ISS-N1) as its target.
A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy.
TLDR
Benefit showing reduced endomysial fibrosis, reduced central nucleation, more normal fiber size distribution with muscle hypertrophy, especially at high dose is encouraging for treatment of dystrophin-deficient muscle diseases.
Disease Mechanisms and Therapeutic Approaches in Spinal Muscular Atrophy
TLDR
SMA is emerging as an RNA disease not limited to motor neurons, but one that involves dysfunction of motor circuits that comprise multiple neuronal subpopulations and possibly other cell types, and offers unprecedented promise for the treatment of this still incurable neurodegenerative disease.
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