Three Publications Feature Exciting Findings in Dysferlinopathy
In this blog post below, we’re highlighting 3 publications that we feel would be interesting to dysferlin research and clinician communities.
StitchR Technology Enables the Creation of Full-Length Dysferlin Proteins
The above illustration depicts StitchR’s dual vector gene therapy approach for large genes. Credit: Scriptr Global
This study, led by Doug Anderson, PhD, from the University of Rochester School of Medicine and Dentistry, demonstrates how the innovative StitchR technology, short for “stitch RNA,” can restore the full-length expression of large proteins like dysferlin and dystrophin. It achieves this by “stitching” together two RNA fragments of a gene to create a full-length transcript that enables expression of a full-length protein. The intent is to develop the StitchR technology to facilitate gene replacement therapy using multiple viruses to deliver genes that are too big to fit in a single AAV vector. This work is a significant step forward in the development of genetic therapies for Dysferlinopathy (LGMD2B/R2, Myoshi Myopathy) and Duchenne muscular dystrophy.
Link to full article: Ribozyme-activated mRNAtrans-ligation enables large gene delivery to treat muscular dystrophies
Using the Performance of Upper Limb (PUL) Entry Item in Clinical Practice to Determine which Dysferlinopathy Patients are at Risk for Respiratory Impairment
This article utilized patient data collected as part of the Clinical Outcome Study (COS) for Dysferlinopathy, led by Volker Straub, MD, PhD, and the team from the John Walton Muscular Dystrophy Research Center at Newcastle University. The article notes that spirometry is the gold standard for diagnosis and monitoring of respiratory impairment but that it is not always easily accessible. Based on patient data modelling that indicates a significant positive relationship between the PUL entry item (shoulder abduction of arms above head) and forced vital capacity (FVC), this study suggests that the PUL entry item can be implemented in clinical practice to screen dysferlinopathy patients for respiratory impairment where spirometry is not readily available.
Link to full article: Performance of upper limb entry item to predict forced vital capacity in dysferlin-deficient limb girdle muscular dystrophy – Neuromuscular Disorders
Pilot Investigations into the Mechanistic Basis for Adverse Effects of Glucocorticoids in Dysferlinopathy
Glucocorticoids are used to reduce inflammation and treat some types of muscular dystrophies but, when administered daily to patients with dysferlinopathy, they have unexpected adverse effects, with accelerated loss of muscle strength. The reason for this is not understood. This study, led by Miranda Grounds, PhD, of the University of Western Australia, proposes some mechanisms that could explain the adverse effects of glucocorticoids in dysferlinopathy.
Link to full article: Pilot investigations into the mechanistic basis for adverse effects of glucocorticoids in dysferlinopathy