Safety, tolerability and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy
Kalyani Madhukar Mali
, Komal Sanjiv Mahajan
Casimersen , muscular dystrophyk
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene resulting in the absence of dystrophin. Casimersen is a phosphorodiamidate morpholino oligomer designed to bypass frameshift DMD mutations and produce internally truncated, yet functional, dystrophin protein in patients amenable to exon 45 skipping. Our primary study objective was to evaluate safety and tolerability of casimersen; the secondary objective was to characterize the plasma pharmacokinetics. INRODUCTION: - In DMD, frameshift or nonsense mutations in the DMD gene prevent the production of functional dystrophin, resulting in progressive, life-shortening disease. Management of DMD has involved a multidisciplinary approach to treat symptoms and modify disease progression; however, there is no cure for the disease [4] Antisense therapy using chemically engineered antisense oligonucleotides (ASOs) complementary to specific mRNA is a prominent method for treating neuromuscular disorders like Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) [5,6]. ASOs can be used for RNA degradation, suppression of translation, or modulation of splicing [ 6]. Standard-of-care therapy for DMD includes the long-term use of glucocorticosteroids [7] One approach that has been investigated in the development of therapies for DMD has been to target restoration of the production of functional dystrophin, including using exon skipping. [4,8,9]. The approval, granted under the US FDA’s Accelerated Approval Program, was based on an observed increase in dystrophin production in skeletal muscle in patients treated with casimersen [10]. Dystrophic muscle is not able to recover enough to overcome this loss, gradually leading to fibrotic remodelling and the replacement of muscle with fat [11] In addition to muscle weakness and loss of ambulation, DMD patients develop respiratory and cardiac weakness, requiring palliative care [12] An increase in dystrophin production is considered reasonably likely to predict clinical benefit; however, clinical benefit, including improved motor function, is yet to be established [13]. Continued approval of casimersen in the treatment of DMD may be contingent on verification of a clinical benefit in confirmatory trials.
"Safety, tolerability and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy", IJSDR - International Journal of Scientific Development and Research (www.IJSDR.org), ISSN:2455-2631, Vol.8, Issue 1, page no.445 - 446, January-2023, Available :https://ijsdr.org/papers/IJSDR2301073.pdf
Volume 8
Issue 1,
January-2023
Pages : 445 - 446
Paper Reg. ID: IJSDR_203446
Published Paper Id: IJSDR2301073
Downloads: 000347192
Research Area: Pharmacy
Country: Jalgaon , Maharashtra , India
ISSN: 2455-2631 | IMPACT FACTOR: 9.15 Calculated By Google Scholar | ESTD YEAR: 2016
An International Scholarly Open Access Journal, Peer-Reviewed, Refereed Journal Impact Factor 9.15 Calculate by Google Scholar and Semantic Scholar | AI-Powered Research Tool, Multidisciplinary, Monthly, Multilanguage Journal Indexing in All Major Database & Metadata, Citation Generator
Publisher: IJSDR(IJ Publication) Janvi Wave
