Review Identifies 23 Factors Affecting Duchenne MD Prognosis
Treatment with glucocorticoids and heart medicines are key factors in determining the prognosis of Duchenne muscular dystrophy (DMD), according to a study.
Results also highlighted genetics as an important factor affecting DMD progression.
The paper, “Prognostic indicators of disease progression in Duchenne muscular dystrophy: A literature review and evidence synthesis,” was published in the journal PLOS One. The study was funded by PTC Therapeutics.
Scientists from PTC and other institutions conducted a review of the scientific literature seeking to identify prognotic factors for DMD — that is, factors that have a statistically significant effect on disease outcomes. In total, the review included 135 studies, covering 25,610 people with DMD from 18 countries on six continents.
The analysis identified 23 factors that influence the overall prognosis of DMD. Some of these were endogenous factors — unchangeable clinical and biological traits like age at diagnosis, age at onset of symptoms, genetics, height, and body weight.
Among these endogenous factors, genetics — including the specific type of Duchenne-causing mutation in the DMD gene, as well as other genetic factors that can influence the disease progression — were highlighted as core factors that affect the disease prognosis.
“Although more research is needed to quantify the impact of specific modifiers and mutations, emerging data show that these genetic aspects may play a non-trivial role in the overall progression of the disease,” the researchers wrote. “These findings underscore the importance of collecting genetic data from DMD patients as part of studies and patient registries.”
Other identified prognostic factors were exogenous, meaning related to external factors. Most of these involved treatment or care of DMD that can affect outcomes, including a number of medications, surgeries, and ventilation support.
In particular, treatment with glucocorticoids, a type of corticosteroid that is a mainstay of standard DMD treatment, was associated with better outcomes across a range of measures.
“This core exogenous factor was found to significantly impact a wide range of disease progression outcomes, including loss of independent ambulation, lower extremity and motor function, muscle strength, respiratory health and function, survival, and upper extremity function,” the researchers wrote. Glucocorticoid treatment also was tied to better heart health and a lower risk of developing scoliosis, but the quality of evidence was not as strong.
Another core treatment factor affecting outcomes was the use of cardiac medication (treatments aiming to improve heart health). “Bearing in mind that cardiomyopathy [heart muscle disease] has emerged as one of the leading causes of death in the aging DMD population in the presence of the routine use of mechanical ventilation support, the significance of this indicator should not be underestimated,” the team wrote.
A noted limitation of this study, according to the researchers, is that this analysis was only designed to identify factors that affected the course of progression of DMD, in a statistical sense — irrespective of how large or clinically meaningful the impact might be. “This means that it is not possible to discern the relative clinical importance, or relevance, of included indicators,” the scientists wrote.