Analysis of pharmacological properties and clinical treatment principles of golodirsen

Golodirsen (golodirsen) is a drug used for Duchenne Muscular Dystrophy (Duchenne Muscular Dystrophy, The main mechanism of action of antisense oligonucleotide drugs for patients with DMD is to promote the expression of partially functional dystrophin (dystrophin) by skipping the 53 exon mutation in the DMD gene. DMDPatients with DMD gene defects lead to the loss or abnormal function of dystrophin, resulting in progressive muscle atrophy and decreased strength. Gorodison directly corrects gene mutation defects through molecular-level intervention, which is a typical representative of targeted molecular therapy.

In terms of pharmacological properties, Golodisen is a chemically modified phosphate antisense oligonucleotide, which can efficiently bind to the specific exon sequence of pre-gene DMDmRNA in cells, thereby regulating the splicing process. By skipping exon No. 53, the expression of partially functional dystrophin is produced, making the protein length close to normal levels, thereby restoring some muscle fiber functions. The drug is highly targeted and does not interfere with the expression of other genes. When administered clinically through intravenous infusion, it can reach an effective concentration in muscle tissue and ensure therapeutic effects.

The principle of clinical treatment is mainly based on precise intervention of DMD gene defects. Gorodison targets patients with exon 53 deletion mutations and can delay muscle degeneration and loss of function by restoring part of dystrophin expression. Multiple clinical trials have shown that patients who use Golodisen for a long time have a certain improvement trend in muscle strength and motor function scores, and at the same time, the expression level of dystrophin increases significantly. This mechanism provides DMD patients with a causal treatment method based on molecular targets, which has a clearer treatment logic than traditional symptomatic supportive treatment.

In terms of safety, Golodisen is generally well tolerated, with the most common adverse reactions including infusion-related reactions, fever and mild gastrointestinal discomfort. Since its mechanism of action is gene-level intervention, long-term efficacy still needs to be continuously observed, but current clinical data shows that use at standard doses can effectively increase dystrophin expression, slow down muscle degeneration, and improve patients' motor function and quality of life. The pharmacological properties and clinical principles of Gorodison provide scientific basis for the precise treatment of DMD and also provide a demonstration for the future development of gene-targeted therapy.

Reference materials:https://trial.medpath.com/drug/approvals/fda/7256cda011e3383a