Researchers at
Children’s National Hospital in the US have developed a promising new gene
therapy for limb-girdle muscular dystrophy (LGMD) 2B.
The disorder, which causes muscle weakness in
various core parts of the body, is a rare genetic condition that affects less
than one in 100,000 but has debilitating consequences such as losing the
ability to walk and carry out everyday tasks. Scientists have successfully
addressed the primary cellular deficit associated with LGMD2B via pre-clinical
gene therapy that consists of a single injection of a low dose of a gene
therapy vector. In their studies, experts found that this approach caused
injured muscle fibres to repair, reducing degeneration and enhancing muscle
function.
The treatment was found to be safe, effective in
attenuating fibro-fatty muscle degeneration, and successful in restoring
myofibre size and muscle strength, according to the study published in the
Journal of Clinical Investigation.
A genetic mutation of the large gene, dysferlin,
impacts muscle health and means that affected individuals experience difficulty
walking, climbing stairs and getting out of chairs, etc. This new treatment
approach avoids the need to package a large gene, such as dysferlin, or give a
large vector dose to target the muscles – thus avoiding common problems
encountered in treatments for the condition. Highlighting
the benefits of this innovative approach, senior investigator of the Center for
Genetic Medicine Research at Children’s National Hospital, Jyoti K Jaiswal, MSc
PhD, commented, “Currently, patients with LGMD2B have no gene or drug-based
therapies available to them, and we are amongst the few centres developing
therapeutic approaches for this disease.
We are working to further enhance the efficacy of
this approach and perform a longer-term safety and efficacy study to enable the
clinical translation of this therapy.”
Expanding upon the challenges the team has managed
to avert using their approach, lead author Daniel Bittel, DPT, PhD said:
“Increased muscle degeneration necessitates greater muscle regeneration, and we
found that improved repair of dysferlin-deficient myofibres by hASM-AAV reduces
the need for regeneration, causing a two-fold decrease in the number of
regenerated myofibres.”
Highlighting the possible wider implications of
their work, Sreetama Sen Chandra, PhD, who was a research postdoctoral fellow
at Children’s National at the time of the study and served as co-lead author,
added: “These findings are also of interest to patients with Niemann-Pick
disease type A since the pre-clinical model for this disease also manifests
poor sarcolemma repair.”
World Journal of Case Reports and Clinical Images (ISSN 2835-1568)
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