Startle responses in Duchenne muscular dystrophy: a novel biomarker of brain dystrophin deficiency

Duchenne muscular dystrophy (DMD) can affect the brain as well as the muscles and heart. This can lead to learning or mental health problems, such as anxiety, in at least half of individuals with DMD. With current DMD care, life-expectancy is improving. Mental health problems like anxiety can however significantly impact the lives of boys and young men with DMD, particularly as they become older and begin to manage their own health care. Therefore, it is important to understand the basis for anxiety in DMD to optimise their healthcare and quality of life. 

The paper titled “Startle Responses in Duchenne Muscular Dystrophy: A Novel Biomarker of Brain Dystrophin Deficiency” explores the potential of a novel biomarker called startle responses to assess brain dystrophin deficiency in individuals with DMD. 

In typical people with anxiety the brain’s ‘fear system’ can be dysfunctional, and we know that the areas of the brain involved in the fear system are affected in DMD. Previous studies have also shown that mice with DMD have a markedly increase response to stressful situations compared to normal mice. When young DMD mice are treated with genetic therapies, these abnormal stress related responses improve. In this study we wanted to investigate whether the fear system which is closely correlated with anxiety is affected also in boys with DMD, and provide a more quantifiable measure of this response.  

In order to identify objective measures of excessive response to stimuli that normally would not cause a substantial stress to individuals, we devised a particular test in which a visual or auditory stimulus leads to a mild level of stress. This is measured with the amount of sweat produced or variability of heart rate. Any even minimal change in the environment generates in all of us minimal changes of these parameters, and in this study we identified very precise measurements of these variables. 

What we found is that boys with DMD responded with much greater level of response- hence of stress- compared to boys without DMD.  

This is the first time this has been shown and is important for two reasons: 

1. It indicates that individuals with DMD have an underlying predisposition to experiencing anxiety symptoms, over and above any situational stressors that occur as a consequence of living with a physically disabling, life-limiting condition. This also suggests that some aspects of the brain-related symptoms might be reversible with genetic therapies, as is the case in DMD mice.  

1. As the test we used in this study is intimately related on how specific areas of the brain function, it could be used as a biomarker of successful treatment in future clinical trials if treatments for the brain aspects of DMD are tested.