Indications
Golodirsen is specifically indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who possess a confirmed mutation of the DMD gene amenable to exon 53 skipping. The continued approval of Golodirsen by the FDA is dependent upon further clinical trials to conclusively establish its therapeutic benefit.
Pharmacodynamics
Golodirsen functions by masking specific genetic mutations, triggering a cascade of molecular events that address Duchenne Muscular Dystrophy in approximately 8% of patients. It plays a crucial role in indirectly promoting the production of dystrophin, a vital protein essential for proper muscle function. Although it remains uncertain whether Golodirsen enhances motor function, ongoing clinical trials aim to evaluate its potential clinical benefits. It is important to note that, although nephrotoxicity has not been confirmed in clinical trials for Golodirsen, similar compounds in the morpholino antisense oligonucleotide class have exhibited nephrotoxic effects; therefore, renal function should be closely monitored during therapy.
Absorption
Administered intravenously, Golodirsen is likely rapidly absorbed into the bloodstream. Pharmacokinetic studies of similar agents such as eteplirsen have shown that maximum plasma concentrations (Cmax) are reached within approximately 1.1 to 1.2 hours following the initiation of infusion, across a dosing spectrum of 0.5 mg/kg/week to 50 mg/kg/week.
Metabolism
Golodirsen is characterized by minimal metabolic transformation. In a pharmacokinetic study, no metabolites were detected in either plasma or urine, indicating that the drug is not extensively metabolized.
Mechanism of Action
Golodirsen functions by targeting exon 53 of the dystrophin pre-mRNA within the DMD gene, effectively omitting this segment during mRNA processing. This specific mechanism alters the mRNA from an out-of-frame to an in-frame sequence, thereby facilitating the production of dystrophin. The resultant dystrophin is not fully functional but can mitigate the severity of Duchenne Muscular Dystrophy. This action repositions the condition toward Becker Muscular Dystrophy, which is associated with a truncated yet partially functional dystrophin protein. Individuals with Becker Muscular Dystrophy typically experience improved muscle function, increased longevity, and enhanced quality of life.
