Some therapeutic advancements are so central to the diseases they treat that they themselves define a specific era in the therapeutic history of the disease, even as physicians continue to search for a definitive cure.
Some therapeutic discoveries have redefined and reinvigorated modern medicine as we know it. Take, for example, the discovery of penicillin, which revolutionized the treatment of microbial infections. Another often-touted example is the discovery of x-rays, and, more broadly speaking, the invention of medical imaging, which is central to the modern medical process from start to finish.
What “era” are we in with regard to the treatment of Duchenne muscular dystrophy (DMD)? This is a potent question to ask, but the answer shifts like sand depending on when it is posed, and to whom.
Read more about DMD etiology
In the Orphanet Journal of Rare Diseases, Szabo and colleagues proposed that we are in the “corticosteroid treatment era” of DMD. Despite the various experimental therapies that are currently the subject of intense clinical research, the mainstay treatment for DMD over the last few decades has been the introduction of systemic corticosteroids, which studies have time and time again confirmed slows disease progression and improves survival.
Characterizing the Impact of Corticosteroid Therapy on DMD Care
Szabo et al sought to study the impact of corticosteroid treatment in a number of DMD disease progression milestones. They conducted a literature review, studying hundreds of studies and choosing to analyze 29.
The research team did an excellent job of defining clinically relevant outcomes of patients with DMD. For example, in terms of ambulation, results indicate that the earliest mean age at which patients lose their ability to ambulate was 9.5 years, with those taking corticosteroids for 3 years or less, while patients who take corticosteroids for 3 years or more lose their ability to ambulate at an earliest mean age of 12.3 years.
However, the benefits of corticosteroid therapy in other health parameters are less clear, especially in terms of mean age of scoliosis, pulmonary function test results, and the need for ventilator support. The difficulty here is that endpoints of studies vary, complicating like-for-like comparisons. Researchers did discover that the mean age of mortality ranged from 18.1 years to 20.0 years in patients who received corticosteroid treatment.
“Additional studies on the ages at occurrence of other important DMD clinical milestones, and the relationships between short-term and long-term outcomes, will be valuable in the continuation of knowledge regarding disease progression in DMD,” Szabo et al concluded.
In Pharmacology & Therapeutics, Iftikhar and colleagues argued for a more expansive view of DMD therapeutics that includes multidisciplinary input and care.
While muscle wasting is a defining characteristic of DMD, the real contributor to mortality is cardiac or respiratory failure, which, as we have seen, usually occurs within the first 3 decades of life. Some form of cardiomyopathy typically manifests within the first decade of life.
Iftikhar and colleagues agree that corticosteroids play a major role in DMD therapeutics today: “Corticosteroids and artificial respirators remain as the gold-standard management of complications of DMD and have significantly extended the life span of DMD patients.”
However, they stress the need for adequate cardiac, pulmonary, orthopedic, nutritional, and psychosocial evaluation in patients with DMD.
So what is likely to be the imminent revolution in DMD therapy? The answer: gene therapy. Gene therapy is promising because it can potentially treat the problem at its very source by restoring the function of dystrophin truncated protein, which should lead to a huge boost in skeletal and cardiac muscle health.
In this regard, antisense oligonucleotides and exon-skipping mechanisms hold significant promise. Their ability to skip mutated exons within pre-mRNA transcripts can help researchers inch closer to a complete cure for the disease.
However, a word of caution: “It is difficult to approach genetic therapy for this condition . . . taking into consideration the large size of the dystrophin gene and the specificity involved with regulation in tissue expression,” Iftikhar et al wrote.
However, looking at the glass half full, we have reasons to be optimistic. First, we currently have a form of therapy (corticosteroids) that have by and large improved clinical outcomes. The immediate therapies that are in the works involve treating the disease at a genetic level, which is the only way to cure the disease.
Read more about DMD treatment
While modern medicine is always in labor for new solutions that take us beyond symptomatic control, as physicians we still need to make sure that we are doing everything possible to delay disability (and mortality). For example, studies indicate that the loss of ambulation is a major factor in patients’ perceived loss of quality of life, and physicians should do all that they can to delay this as much as possible.
“The introduction of gene therapy-based therapeutics is considered a major breakthrough in the improved treatment of DMD and SMA patients,” Iftikhar and colleagues concluded. “Both pharmacological and nonpharmacological management are critical to improving patient outcomes and quality of life.”
Szabo SM, Salhany RM, Deighton A, Harwood M, Mah J, Gooch KL. The clinical course of Duchenne muscular dystrophy in the corticosteroid treatment era: a systematic literature review. Orphanet J Rare Dis. Published online May 22, 2021. doi:10.1186/s13023-021-01862-w
Iftikhar M, Frey J, Shohan MJ, Malek S, Mousa SA. Current and emerging therapies for Duchenne muscular dystrophy and spinal muscular atrophy. Pharmacol Ther. Published online October 29, 2020. doi:10.1016/j.pharmthera.2020.107719