Duchenne muscular dystrophy: overview and future challenges

• Authors: Moh Hasan Machfoed , Valentinus Besin , Mudjiani Basuki , Shirley Ferlina Lasmono

Title variants

PL

Dystrofia mięśniowa Duchenne’a: przegląd literatury i wyzwania w przyszłości

• Languages of publication: EN

Abstracts

EN

Duchenne muscular dystrophy is a muscle disease caused by mutation in the gene that encodes the cytoskeletal protein dystrophin. It is inherited in an X-linked recessive fashion. A number of therapies are continuously being developed to slow down the progression of the disease and increase patients’ life expectancy. Steroid use in Duchenne muscular dystrophy is associated with a lower mortality rate (hazard ratio = 0.24; 95% CI = 0.07–0.91; p = 0.0351). Although recent studies have concluded that prolonged steroid use is associated with short stature and overweight, a meta-analysis of 12 studies has shown that steroids can increase strength, muscle function, and quality of life. Restoration of dystrophin gene expression is the basis of genetically engineered therapies. Potential therapies of this type include exon skipping, the use of recombinant adenoassociated virus which delivers mini-dystrophin, and surrogate gene transfer. In their development, the common challenges are associated with the size of gene product and the origin of dystrophin gene expression. Stem cells are promising for future therapy. Regardless of the challenges and controversies associated with stem cells, several clinical trials show an increase of  muscle strength in patients who have received such therapies.

PL

Dystrofia mięśniowa Duchenne’a jest chorobą dziedziczoną w sposób recesywny, sprzężoną z chromosomem X, spowodowaną mutacjami w genie DMD kodującym białko dystrofinę. Obecnie opracowywane terapie mają na celu spowolnienie progresji choroby oraz przedłużenie przeżycia pacjentów. Leczenie z użyciem kortykosteroidów wiąże się z mniejszym ryzykiem zgonu (współczynnik ryzyka = 0,24; 95% CI = 0,07–0,91; p = 0,0351). Choć ostatnio prowadzone badania wykazały, że długotrwałe stosowanie kortykosteroidów przyczynia się do niskiego wzrostu i nadwagi, w metaanalizie 12 badań stwierdzono ich wpływ na zwiększenie siły mięśni, poprawę ich funkcji i lepszą jakość życia chorych. Odzyskanie ekspresji genu dystrofiny stanowi podstawę terapii genowych, w  tym metody pomijania zmutowanego egzonu (tzw. exon skipping), zastosowania rekombinowanych wirusów związanych z adenowirusami w celu wprowadzenia minidystrofiny oraz wymiany genu (gene transfer). Trudności związane z terapiami genowymi wiążą się z rozmiarem genu oraz pochodzeniem ekspresji dystrofiny. Inną obiecującą terapię stanowią komórki macierzyste. Bez względu na trudności i kontrowersje związane z leczeniem tego typu kilka badań klinicznych wykazało, że poprawia ono siłę mięśniową u osób z chorobą Duchenne’a.

Keywords

EN

Duchenne muscular dystrophy; genetic engineering; stem cells; therapy

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Aktualności Neurologiczne
• Year: 2017
• Volume: 17
• Issue: 3
• Pages: 144–149

Contributors

author

Moh Hasan Machfoed

• Department of Neurology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

author

Valentinus Besin

• Department of Neurology, Faculty of Medicine, University of Surabaya, Surabaya, Indonesia

author

Mudjiani Basuki

• Department of Neurology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

author

Shirley Ferlina Lasmono

• Department of Pediatrics, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

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• Document Type: article