Emerging therapies for Duchenne muscular dystrophy
Theodora Markati1, Maryam Oskoui2, Michelle A Farrar3
1MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
The Lancet. Neurology
|July 19, 2022
Summary
Glucocorticoids are the only proven treatment for Duchenne muscular dystrophy, despite side effects. Ongoing research explores gene therapies and other compounds, but clinical development faces challenges due to disease rarity and variability.
Area of Science:
- Neurology
- Genetics
- Pharmacology
Background:
- Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by the absence of functional dystrophin in muscle cells.
- Current treatments include glucocorticoids, which slow disease progression but have adverse effects, and several approved compounds with pending efficacy data.
Purpose of the Study:
- To review the current therapeutic landscape for Duchenne muscular dystrophy.
- To highlight the challenges and future directions in clinical development for DMD.
Main Methods:
- Review of current literature on Duchenne muscular dystrophy treatments.
- Analysis of approved therapies, ongoing clinical trials, and emerging therapeutic strategies.
- Discussion of challenges in clinical development, including disease rarity and variability.
Main Results:
- Glucocorticoids remain the only unequivocally effective treatment for slowing DMD progression.
- Several compounds have gained regulatory approval in specific regions, while others have failed to meet endpoints in late-phase trials.
- Numerous compounds targeting various pathways are in ongoing clinical development.
Conclusions:
- The therapeutic landscape for DMD is complex, with multiple compounds and approaches under investigation.
- Overcoming clinical development challenges may involve sensitive biomarkers, natural history data, and improved trial designs.
- Future advancements aim to address the unmet needs in Duchenne muscular dystrophy treatment.
Related Concept Videos
01:21Satellite Stem Cells and Muscular Dystrophy
2.0K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
2.0K
01:26Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
749
Directly acting muscle relaxants like dantrolene and botulinum toxin (BoNT) have distinct mechanisms and applications. Dantrolene, a hydantoin derivative, acts on the ryanodine receptor (RYR1) in skeletal muscle cells. RYR1 are calcium channels present at the sarcoplasmic reticulum membrane. In response to excitation, they release calcium ions from the sarcoplasmic reticulum to the cytosol. Calcium promotes actin-myosin-mediated contraction of muscles.
The binding of dantrolene to the RYR1...
The binding of dantrolene to the RYR1...
749
01:31Skeletal Muscle Relaxants: Therapeutic Uses
608
Skeletal muscle relaxants are used to relax muscle tone and alleviate painful muscle contractions. However, the choice of skeletal muscle relaxants depends on the duration of the surgical procedure in order to minimize potential side effects. Skeletal muscle relaxants like neuromuscular blocking agents [NMBAs] are commonly employed as adjuvants alongside general anesthetics in clinical settings. NMBAs are also used to maintain controlled ventilation during surgery of the larynx or pharynx...
608