A recent editorial focusing on NMDs (neuromuscular disorders) was published in the journal Disease Models & Mechanisms. The editorial highlights a special issue of the journal devoted to building on basic scientific research in order to develop new therapies and diagnostics.
NMDs are diverse genetic diseases that involve the peripheral nerves and restrict the muscle’s ability to function.
The skeletal muscles are generally affected in NMD. In Duchenne muscular dystrophy, the mutation may be a result of insufficient brain-specific dystrophin isoforms, leading to cognitive and behavioral deficits.
Overall, the treatment options are limited due to the rarity and diversity of NMD disorders. Other negative factors include complicated genetics and the excessive amount of muscle tissue that must be treated. This creates a scarcity of treatments for NMDs and limits their off-label availability.
NMD’s rarity also poses a problem for clinical trials that must enroll a specific number of evaluable patients with prior data. The success of these trials therefore depends on the reliability of preclinical studies.
The special issue of the journal presents articles and reviews focusing on biomarkers that track disease, cellular mechanisms, mouse models, the importance of preclinical studies, and validation of data. It also discusses some of the difficulties of moving therapeutic strategies into the clinic.
Much of the value of preclinical studies is dependent upon the availability of animal and cell models that can give an accurate summary of various aspects of the disease.
The expedited production of appropriate animal and cell models has been facilitated by CRISPR/Cas9 and versatile stem cells called pluripotent stem cells.
The previous decade has seen improvement in working with humanized animal models carrying human-specific genetic lesions. Committees have been established that assess preclinical data prior to a drug’s moving forward to a clinical trial.
Two guest editors explain the advantages of developing humanized mouse models for personalized medicine which targets human mutations. The editors explain the usefulness and potential of these models using as an example a recently created model that was created for Duchenne muscular dystrophy.
The editors (Aartsma-Rus and van Putten, 2019) discuss genetic mutations that are associated with thousands of inherited diseases. The expansion of DNA sequencing now makes it feasible to diagnose many more genetic diseases. Gene therapy is used to provide a copy of the missing genes in tissues and cells that are affected by a mutation.
Recently, genome editing has been used to modify the disease-causing gene. Most genetic diseases are the result of various mutations or mutation types. It is for that reason that treatment must be custom made to target specific mutations.
There have been some amazing advances in the neuromuscular field in recent years and these have been well-documented in the Special Issue.
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