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Page 245 Angelini. J Transl Genet Genom 2024;8:244-8 https://dx.doi.org/10.20517/jtgg.2024.29

atypical cases, and Becker muscular dystrophy (BMD), as well as carriers. However, identifying appropriate
primary outcomes and tools remains a challenge in DMD research. Tests such as the 6-minute walk test
(6MWT), Gross Motor Function Measure (GMFM), North Star Ambulatory Assessment (NSAA), timed
function tests, quality of life assessments, and daily activity monitoring have all been utilized but yield
varying rates of success in trials.

Early indicators of DMD may include delayed motor milestones, with some children not walking until 18
months of age, muscle weakness, particularly in the pelvic muscles, enlarged calves, and gait abnormalities.
Patients often exhibit a waddling gait and have difficulty rising from the floor, known as Gowers’ sign.

Steroid therapy remains the cornerstone of treatment for DMD, regardless of the specific dystrophin gene
variant in affected children. Corticosteroids, such as prednisone and deflazacort, are commonly used to slow
the progression of muscle weakness in DMD. While disease-modifying therapies are emerging, they still
present significant limitations and might be applicable only to selected groups of DMD patients with
different pathogenic variants. These evolving treatments include exon-skipping drugs (e.g., eteplirsen,
golodirsen) and gene therapies that are undergoing trials with promising outcomes.

Steroids are currently the only treatment proven to slow disease progression, despite significant
advancements in other therapeutic strategies. However, long-term steroid use poses risks of adverse
[1-3]
effects . Gene editing using the CRISPR system is a promising therapeutic approach, along with other
investigational treatments such as exon skipping therapy, microdystrophin therapy, stop codon readthrough
therapy, and utrophin upregulation. However, challenges such as delivery efficiency, off-target mutagenesis,
and long-term maintenance of dystrophin must be addressed. In particular, further studies focusing on the
safety and accuracy of CRISPR are necessary before clinical translation. Overall, the latest advances in DMD
treatment involve gene therapies, exon skipping, and gene or cellular therapies.

However, despite recent advances in translational research and general healthcare, DMD, a muscle-wasting
disease, remains 100% fatal. Individuals born with Duchenne typically do not live beyond their mid-20s.
Nevertheless, with multiple treatments now available, some are entering their fourth decade, marking a
critical transition from childhood to adult cure, which presents a significant challenge. Developing a
treatment, and ultimately a cure, is crucial. Apart from muscular dystrophy, bone loss is a prominent
symptom of this genetic disorder. Bisphosphonates are commonly prescribed to address this issue in DMD
patients. Choosing the appropriate therapy has demonstrated the potential to improve muscle dysfunction
and prevent future bone loss.

Additionally, Dystrophinopathies, including DMD and Becker muscular dystrophy (BMD), are X-linked
conditions resulting from out-of-frame or in-frame variants of the Dystrophin gene. A drug-modifying
approach to treating DMD should decrease inflammation and fibrosis caused by dystrophin deficiency, and
promote muscle satellite cell regeneration and their maturation into myofibers that might ultimately
improve muscle strength and functional performance.

Remarkably, patients carrying the 1,220 A to G (Asn363Ser - N363S) polymorphism in the steroid receptor
had longer deambulation before becoming wheel-chair bound. This indicates a better steroid response in
[1]
DMD patients, resulting in a more effective treatment profile. The efficacy of a novel steroid, deflazacort
(DF), was assessed through a three-year, double-blind controlled trial, where DMD patients were treated
with either deflazacort (DF) at 2.0 mg/kg every other day or a placebo. The DF group showed progress on
the GSGC scale and remained ambulant for over a year, longer than the placebo group. DF has been used in