What are the treatments for Duchenne Muscular Dystrophy (DMD)?
The therapeutic management of Duchenne Muscular Dystrophy is fundamentally symptomatic, based on a set of protocolized measures whose objective is to improve the functionality and quality of life of patients, delay and treat complications, and prolong survival. (Nascimiento et al. 2019)
Although some treatments have seen short-term success, the remainder focuses on the disease’s symptoms and effects rather than the underlying genetic origin, and none have yet healed long-term dystrophin protein expression.
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Nonetheless, several experiments have recently combined CRISPR/Cas9 gene editing with cell therapy to produce more pronounced and long-lasting therapeutic results. (Pini et al. 2017)
Is genome editing the future for the treatment Duchenne muscular dystrophy?
CRISPR/Cas9 (clustered regularly interspaced palindromic repeats) is a gene-editing technique that is causing significant disruption in biomedical science. It allows scientists to rapidly, efficiently, and easily fix errors in the genome and toggle on or off genes in cells and animals. (Redman et al. 2016)
As mentioned above, Monkol Lek, an Assistant Professor in the Department of Genetics at Yale School of Medicine, and his collaborators are planning one of the first CRISPR clinical trials for DMD.
This research is built around a single patient Terry Horgan is the subject of Lek’s investigation. Terry has bravely battled the disease for over 25 years in the hopes of obtaining a cure that will allow him to pause or reverse his illness.
Read Also: First CRISPR Trials on Humans Are Now Being Implemented in the US
Terry’s DMD gene has an exon one deletion that affects the muscle-specific form. However, there are two other “types” of DMD genes that could be stimulated instead. Their target, according to Lek, is to activate one of these forms, the cortical isoform, within skeletal muscle cells to compensate for the exon one mutation.
While Terry’s therapy is specific for him, it has the potential to transform the medical environment for those with DMD.
References
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Gao, Q. Q., & McNally, E. M. (2015). The Dystrophin Complex: Structure, Function, and Implications for Therapy. Comprehensive Physiology, 5(3), 1223–1239. https://doi.org/10.1002/cphy.c140048
Giliberto, F., Radic, C. P., Luce, L., Ferreiro, V., de Brasi, C., & Szijan, I. (2014). Symptomatic female carriers of Duchenne muscular dystrophy (DMD): genetic and clinical characterization. Journal of the neurological sciences, 336(1-2), 36–41. https://doi.org/10.1016/j.jns.2013.09.036
Hendriksen JGM, Vles JSH. Neuropsychiatric disorders in males with duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive-compulsive disorder. J Child Neurol. 2008;23(5):477–81.
Nascimento Osorio, A., Medina Cantillo, J., Camacho Salas, A., Madruga Garrido, M., & Vilchez Padilla, J. J. (2019). Consensus on the diagnosis, treatment and follow-up of patients with Duchenne muscular dystrophy. Consenso para el diagnóstico, tratamiento y seguimiento del paciente con distrofia muscular de Duchenne. Neurologia (Barcelona, Spain), 34(7), 469–481. https://doi.org/10.1016/j.nrl.2018.01.001
Pini, V., Morgan, J. E., Muntoni, F., & O’Neill, H. C. (2017). Genome Editing and Muscle Stem Cells as a Therapeutic Tool for Muscular Dystrophies. Current stem cell reports, 3(2), 137–148. https://doi.org/10.1007/s40778-017-0076-6
Redman, M., King, A., Watson, C., & King, D. (2016). What is CRISPR/Cas9?. Archives of disease in childhood. Education and practice edition, 101(4), 213–215. https://doi.org/10.1136/archdischild-2016-310459
Team Led by Monkol Lek Advances Past Pre-IND Phase with DMD Gene Therapy. (2021). Retrieved 10 May 2021, from https://medicine.yale.edu/genetics/news-article/team-led-by-monkol-lek-advances-past-pre-ind-phase-with-dmd-gene-therapy/
