World Duchenne Awareness Day 2020: Duchenne and the Brain
Today, 7th September 2020, is World Duchenne Awareness Day.
The theme this year is Duchenne and the Brain.
As well as affecting muscles in the body, Duchenne Muscular Dystrophy can also affect the brain. The effect of DMD on the brain is different in every child.
Around a third of patients with DMD show some learning difficulties and behavioural problems. For many patients and their families, these can affect family life more than their muscle problems.
Duchenne UK has FREE resources available to the DMD community to help you learn more about learning difficulties and behavioural problems related to Duchenne:
On p75&76 you will find lots of information on “How DMD affects children’s brains and education”.
Families in the UK can also order a FREE printed copy of the DMD Family Folder
- Order a FREE copy of Janet Hoskin's book: A Guide to Duchenne Muscular Dystrophy: INFORMATION AND ADVICE FOR TEACHERS AND PARENTS
This guide brings together chapters by a range of experts in DMD aimed at supporting young people and their families as they move through school and college. It is not primarily aimed at the physical progression of DMD but rather focuses on learning and behaviour challenges.
There has been much less research in to Duchenne and the brain, compared to research into other areas of DMD.
“We were so occupied studying muscles, we almost forgot to focus on dystrophin in the brain,” said Prof. Francesco Muntoni from Great Ormond Street Hospital for Children NHS Foundation Trust in London, when launching the BIND (Brain Involvement iN Dystrophinopathies) project earlier this year.
The BIND project is the first project of this scale looking in to the involvement of the brain and how this impacts the lives of patients and their families. It’s an EU Funded project connecting 19 European partners, including UK representation by Prof. Francesco Muntoni from Great Ormond Street Hospital for Children NHS Foundation Trust in London. Prof. Francesco Muntoni is the BIND project coordinator and responsible for the scientific management of the ?project.
The ultimate goal of this project is to improve understanding and measurement of dystrophin in the brain, thus working towards better treatments, care and outcomes for all those living with DMD and BMD. Find out more here
Duchenne UK is pleased to be funding a project to investigate whether or not a treatment known as exon skipping can help restore dystrophin in the brain. The process is known as antisense oligonucleotide (AON)-mediated exon-skipping.
In October 2018, Duchenne UK awarded £45,000 to the team at Leiden University Medical Center to investigate the use of antisense oligonucleotide (AON)-mediated exon-skipping to treat the brain of a DMD animal model system.
We spoke to Dr Maaike Van Putten at Leiden University Medical Center to get an update on the project:
Hello Dr. Maaike van Putten, can you introduce yourself?
I am Dr. Maaike van Putten, researcher at the department of Human Genetics at the Leiden University Medical Center, located in the Netherlands. Since 2007, I have focused my research on studying the role of dystrophin in Duchenne muscular dystrophy (DMD) mouse models, and am an expert in exon skipping therapy. Currently, I devote my research time to investigating the role of dystrophin in the brain, and understanding the potential of restoring dystrophin expression in the brain.
Could you explain how DMD affects the brain?
DMD is caused by mutations in the dystrophin gene, which prevents the production of the protein dystrophin. Dystrophin is however not only expressed in muscle; there are also several brain specific dystrophins, differing in size. Two of these are the same size as the muscle dystrophin, while the other two are shorter. All DMD patients lack the long dystrophins in the brain and the muscle, while depending on the position of the mutation, patients can lack one or both shorter dystrophins in the brain as well.
Absence of these brain specific dystrophin proteins can lead to cognitive and behavioural difficulties. It is thought that the number of dystrophins lacking in the brain correlates to the severity of the cognitive and behavioural problems.
What is the project you're working on for Duchenne UK?
Exon skipping therapies have been conditionally approved in the USA and Japan to restore dystrophin expression in muscle: Exon 51 skipping is approved in the USA (Sarepta; eteplirsen), while exon 53 skipping has been approved in the USA (Sarepta; golodirsen) and Japan (viltolarsen, developed by Nippon Shinyaku).
Unfortunately, these exon skipping treatments cannot cross the blood-brain-barrier when administered as an injection, which means the treatment does not reach the brain. For this reason, current exon-skipping therapies are not effective at treating the learning difficulties and cognitive effects associated with DMD.
My DUK project is designed to try to restore the long dystrophin in the brain of mice, to study whether this improves behaviour and learning.
When might we see results from the project?
I aim to finalize the project within a year.
If the project does show promise, what would be the next steps?
If we find that the exon skipping treatment can sufficiently restore dystrophin expression in the brain, longer term safety and efficacy studies should take place. These studies will be required to understand the full potential of dystrophin restoration in the brain on brain pathology and behaviour. I am currently part of BIND, the international collaboration to work on this with other European researchers.
Thank you Dr Maaike Van Putten!
We look forward to updating you on the progress of this research. If you have any questions please email [email protected]
NOTES FOR EDITORS
What is Duchenne Muscular Dystrophy?
Duchenne muscular dystrophy (DMD) is the most common fatal genetic disease diagnosed in childhood. Children born with DMD cannot produce the protein dystrophin which is vital for muscle strength and function. Muscle weakness starts in early childhood. Many use a wheelchair by around the age of 12. As deterioration continues it leads to paralysis and early death, often in their 20s. It almost exclusively affects boys. There is no treatment or cure. In the UK there are around 2,500 boys affected and around 300, 000 worldwide. It is classified as a rare disease.
Who are Duchenne UK?
Duchenne UK has one clear aim – to end Duchenne, a devastating muscle-wasting disease. As the leading Duchenne charity in the UK, we connect the best researchers with industry, the NHS and families to challenge every stage of drug development to make the incurable, curable. Together, we will find treatments and cures for this generation of patients with Duchenne.
Our president is HRH The Duchess of Cornwall. Our patrons include the broadcasters Krishnan Guru-Murthy and Mary Nightingale, and the sports stars Owen Farrell, Kris Radlinski and Andy Farrell.
We need your help, because we need to keep funding promising new research.
How to donate?
Duchenne UK is entirely reliant on donations to fund research for treatments and a cure to DMD. This can be done via:
- Direct Debit – Duchenne Direct
- Individual Donation – Donate
- If you are a family or friend affected by DMD you can set up your own fund with Duchenne UK – Family and Friend Funds
- Take part in one of our fundraising events – Events
- Text DUCHENNE to 70085 to donate £5. This costs £5 plus a std rate msg.
For more information visit www.duchenneuk.org
Published on 7 September 2020Share this article Categories Patient care & support