DUCHENNE KAS DİSTROFİSİNDE YENİ UFUKLAR: NÜKLEER FAKTÖR KAPPA YOLU VE VAMOROLON’UN TEDAVİYE ETKİLERİ

Year 2025, Volume: 49 Issue: 3, 915 - 927, 19.09.2025

Gülsüm Helvacı , Aylin Bilgin

https://doi.org/10.33483/jfpau.1601594

Abstract

Amaç: Duchenne kas distrofisi (DMD), distrofin eksikliği nedeniyle kas dejenerasyonu ve zayıflığına yol açan X'e bağlı bir hastalıktır. Tedavide amaç, hastalığın ilerlemesini yavaşlatmak ve yaşam kalitesini artırmaktır. Nükleer faktör kappa B (NF-κB) yolu, inflamasyonla ilişkili genlerin düzenlenmesinde rol oynar ve bu yolun hedeflenmesi tedavi stratejilerinden biridir. Glukokortikoidler NF-κB yolunu inhibe ederek etki gösterse de, osteoporoz, hipertansiyon ve büyüme geriliği gibi ciddi yan etkilere yol açabilir. 2023’te FDA onayı alan vamorolon sentetik bir kortikosteroiddir. Vamorolon glukokortikoid reseptörlerini (GR) hedefler, ancak glukokortikoid yanıt elemanını (GRE) aktive etmez. Bu sayede, geleneksel kortikosteroidlere göre yan etkileri daha azdır. Bu derleme, NF-κB yolunun DMD tedavisindeki rolünü ve vamorolonun etkililik ve güvenlilik profilini değerlendiren çalışmaları incelemeyi amaçlamaktadır.
Sonuç ve Tartışma: Geleneksel glukokortikoidler NF-κB’yi inhibe ederek DMD tedavisinde etkinlik gösterir, ancak ciddi yan etkilere neden olabilirler. Vamorolon, NF-κB yolunu benzer şekilde inhibe ederken GRE aktivasyonunu tetiklemediği için geleneksel glukokortikoidlere kıyasla daha az yan etki oluşturur. Klinik çalışmalar, vamorolon’un etkililiğinin glukokortikoidlere benzer olduğunu, ancak yan etkilerinin daha az olduğunu göstermiştir. Vamorolon, DMD tedavisinde geleneksel glukokortikoidlere alternatif olarak umut vaat eden bir ilaçtır.

Keywords

Duchenne kas distrofisi , glukokortikoidler , nükleer faktör kappa , vamorolon

NEW HORIZONS IN DUCHENNE MUSCLE DYSTROPHY: NUCLEAR FACTOR KAPPA PATHWAY AND THERAPEUTIC EFFECTS OF VAMOROLONE

Abstract

Objective: Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by muscle degeneration and weakness due to dystrophin deficiency. The primary goal of treatment is to slow disease progression and improve quality of life. The nuclear factor kappa B (NF-κB) pathway plays a role in regulating inflammation-related genes and is a target for therapeutic strategies. Although glucocorticoids act by inhibiting the NF-κB pathway, they can cause serious side effects such as osteoporosis, hypertension and growth retardation. Vamorolone is a synthetic corticosteroid that received FDA approval in 2023. Vamorolone targets glucocorticoid receptors (GR) but does not activate the glucocorticoid response element (GRE). This results in fewer side effects than traditional corticosteroids. This review aims to examine studies evaluating the role of the NF-κB pathway in the treatment of DMD and the efficacy and safety profile of vamorolone.
Result and Discussion: Traditional glucocorticoids show efficacy in the treatment of DMD by inhibiting NF-κB, but they can cause serious side effects. Vamorolone similarly inhibits the NF-κB pathway but does not trigger GRE activation, resulting in fewer side effects compared to traditional glucocorticoids. Clinical studies have shown that the efficacy of vamorolone is similar to glucocorticoids, but with fewer side effects. Vamorolone is a promising alternative to traditional glucocorticoids for the treatment of DMD.

Keywords

Duchenne muscular dystrophy , glucocorticoids , nuclear factor kappa , vamorolone

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