Brain Involvement in Dystrophinopathies (WP5) Part 2
Research type
Research Study
Full title
Brain Involvement in Dystrophinopathies (BIND): Deep functional phenotyping of Duchenne muscular dystrophy and Becker muscular dystrophy patients (WP5)
IRAS ID
289849
Contact name
Francesco Muntoni
Contact email
Sponsor organisation
UCL Great Ormond Street Institute of Child Health
Duration of Study in the UK
2 years, 3 months, 31 days
Research summary
Research Summary -
Intellectual disability and neurobehavioural comorbidities affect at least 50% of the individuals with Duchenne muscular dystrophy (DMD), which, although a rare genetic disease, is the most common form of muscular dystrophy in childhood. Several studies have documented that 25% of the DMD population has intellectual disability with recent studies suggesting that autism and clinically relevant hyperactivity affects 20% and 25% of DMD boys respectively. A milder allelic variant, named Becker muscular dystrophy (BMD), has similar prevalence in the population and is also associated with variable degrees of central nervous system (CNS) comorbidities, which however have been less well defined.
This study will involve male participants with DMD aged 5-17 years and with BMD aged 5-50 years, who will complete a battery of cognitive and behavioural assessments. The objective is to deep phenotype a cohort of 300 individuals with DMD and BMD, focussing on the cognitive and neurobehavioural aspects of these conditions. A sub-group of patients will also undergo magnetic resonance imaging (MRI) to investigate brain structure, volumetric features, perfusion, functional connectivity and metabolism. This information will then be correlated to the location of the underlying DMD gene mutation. The brain imaging part is also going to involve age and sex-matched controls.
While there have been major improvement on the definition of the genetic basis of the skeletal aspects of dystrophinopathies and their correlation to the DMD genotype, our knowledge on the spectrum of lifespan CNS comorbidities and the precise genotype / phenotype correlations in patients with different DMD mutations is therefore limited. A study looking into the association between different dystrophin isoforms and different CNS manifestations would therefore offer a unique opportunity to unravel the role of specific dystrophin isoforms and the associated circuitries in brain function.
Lay Summary of Results -
The Brain Involvement in Dystrophinopathies (BIND) Study was a major international research project funded by the European Union’s Horizon 2020 programme. Running from October 2021 to June 2024, the study brought together 19 partners from across Europe and Japan, working collaboratively to better understand how Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) may affect the brain.
Although DMD and BMD are genetic muscle disorders, there's growing evidence that dystrophin (the missing or faulty protein in these conditions) is also important for brain function. The BIND study focused on understanding the neurobehavioural aspects of these conditions and how they relate to the specific genetic mutations involved. As the condition is X-linked, only males are affected.
This study involved deep phenotyping male participants with DMD aged 5-17 years and with BMD aged 5-50 years, who completed a set of cognitive and behavioural assessments. The aim of this study was to understand the relationship between DMD and BMD brain comorbidities, and correlate this with the location of the DMD gene mutation which causes the disease. A sub-group of participants also underwent magnetic resonance imaging to investigate if brain structures, blood flow, connectivity between different brain regions and metabolism were affected in these conditions.
Although the BIND study has now finished, data analysis and publication writing are still ongoing. Webinars have been held in different countries including the UK to disseminate findings to families and advocacy groups throughout the project. Two review articles and one workshop report have been published and lay summaries disseminated via the BIND website, and a number of clinical publications are under preparation. Each of these publications will be disseminated to families via the BIND website and the partners advocacy groups. Researchers are continuing to work together to better understand the findings and are exploring new ways to improve diagnosis and care for individuals affected by brain-related challenges in DMD and BMD.
We would like to sincerely thank all the participants and their families who gave their time and effort to take part in the BIND study. Your involvement has made an important contribution to science and will help improve care and support for people living with Duchenne and Becker Muscular Dystrophy.REC name
London - Hampstead Research Ethics Committee
REC reference
21/LO/0631
Date of REC Opinion
27 Oct 2021
REC opinion
Further Information Favourable Opinion