D-Brain

Duchenne Muscular Dystrophy is characterised by out-of-frame gene deletions that abolish the ability to produce dystrophin in muscles and in the brain. Studies have shown that brain dystrophin deficiency results in a neuropsychiatric syndrome in more than 50% of patients and have indicated higher incidence of neurobehavioural comorbidities such as Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorders (ADHD), Obsessive Compulsive Disorders (OCD), Anxiety Disorders and Depressive disorders. These central nervous system (CNS) manifestations of DMD have major implications for the quality of life of the individuals affected. The milder allelic variant Becker Muscular Dystrophy (BMD), is associated with less severe progression of muscle weakness; individuals also experience brain comorbidities but their prevalence and severity in BMD has never been systematically assessed.

It is possible to restore brain-expressed dystrophin through intrathecal administration of antisense oligonucleotides (AONs) in mice, leading to reversal of the neurobehavioural phenotype. This implies aspects of the human neurobehavioural phenotype could be improved in DMD patients following dystrophin restoration in the brain. Clinical trials in boys with DMD are currently being conducted to improve skeletal muscle functioning in DMD, using exon skipping to restore the mRNA reading frame. AONs introduced into the CNS could potentially improve cognitive, behavioural and emotional symptoms associated with DMD and BMD, many of which are believed to result from brain dysfunction secondary to the genetic anomaly. Evaluating the effectiveness of treatment in a clinical trial demands robust clinical outcome measures, including biomarkers of the neurobehavioural phenotype.

The aim of this study is to develop a set of biometric outcome measures that are appropriately sensitive to change, for use in future clinical trials designed to improve neurobehavioural and neurocognitive functioning in DMD/BMD.

 
Primary Outcome Measures

1. Group differences between DMD, BMD and controls in the initial emotional response stimulus of the relevant task

 
Secondary Outcome Measures

1. Group differences between and within groups regarding learning, habituation and extinction in the emotional response task

2. Group differences between groups for the cognitive, behavioural and fine motor skills tasks

3. Group differences between groups for the MRI scans

 
Can I take part?

 
Inclusion Criteria

 
Exclusion Criteria