The annual congress of the Duchenne Parent Project, the Netherlands, was this year held in Heeze, the Netherlands and focused especially on the involvement of the brain in Duchenne muscular dystrophy (DMD). For many Duchenne families the behavioural issues are a major concern. Since the life expectancy is increasing, mental abilities become more and more important for personal development and quality of life.
Dr Jos Hendriksen (Centre for Neurological Learning and Developmental Disorders, Kempenhaeghe) discussed learning and behavioural aspects of DMD. These aspects are often missed, since attention is focused on the physical problems. On average the IQ of Duchenne patients is lower than the general population. ADHD is prevalent among DMD boys (estimates range from 12 to 50%). The big 10 of aspects that could be affected in DMD are: learning tasks to become an automatic habit, working memory, keeping attention, dyslexia, dyscalculia, fear, depression, ADHD, autism and compulsive behaviour. Screening for these factors should become part of the standard care. In the Netherlands they are busy to establish a platform of psychologist and pedagogues to harmonise care.
Prof dr Aartsma-Rus (Leiden University Medical Center) gave an overview the current state of research into treatment options for DMD. Little research has been done on the DMD brain and the effect of therapies on the brain. She gave a general overview of ongoing research. Especially important are the misconceptions about genome editing with CRISPR/Cas9. Even though this shows promising results in cultured cells and mice, she stressed that this is certainly not a cure. It could only turn Duchenne into a milder Becker phenotype. Furthermore effects will really depend on the stage of disease when a patient is treated (the earlier the better). Big hurdles are how to get the compounds in the muscle cells in high enough quantities to be effective (since it is a two-step approach, both compounds need to reach the same cell, which substantially lowers the efficacy), immunity against the viral vector necessary for administration of the compounds and safety concerns. Therefore, it will not become a treatment option in short-term, even if these hurdles can be overcome. For an overview of other treatments see http://www.treat-nmd.eu/dmd/research-overview/introduction. At the moment, since therapeutic options are lacking, currently available care is most important.
Dr Nathalie Doorenweerd (Leiden University Medical Center) talked about the new insights of the role of dystrophin in the brain. The dystrophin protein exists in different forms, which are expressed in different tissues. Not all forms are affected in all patients. Two forms (called Dp140 and Dp71) are found in different parts of the brain. Patients in which one or both forms are missing, show more often brain-related problems (e.g.lower IQ, ADHD, autism).
BrainSTARS (dr Eric Hermans, brain project) is an educational program for children with acquired brain injury, which has originally been developed in the US and is now also used in the Netherlands. Essential parts are 1) psycho-education in the causes and consequences, 2) understanding of the behaviour and possible adaptations and 3) improving cooperation of all persons (parents, doctors, teachers etc) involved in the child’s life. Hereby it is important to adapt the environment to prevent the child from making mistakes instead of only stressing the consequences, since the child would not learn from that. This project could be an inspiration to develop a similar program adapted to DMD. For more information see www.brainline.org/article/brainstars.
Project MAMEM (Multimedia Authoring & Management using your Eyes & Mind; Jaap Ham, TU Eindhoven) aims to develop an internet browser that can be controlled with eye tracking and EEG (brain) recordings. The main goal is to improve the social inclusion of disabled persons. It is currently tested by different patients groups (among which patients with neuromuscular disorders) and healthy persons. Their experiences will be used for further development. For more information see www.mamem.eu.
In the afternoon several workshops were held in parallel.
Bob Averink, Berkenschutse, addressed the importance of going to school for Duchenne patients, but also educational issues that might be faced by Duchenne patients. In the Netherlands during primary and secondary school, laws and schemes exist to help people who need extra support to go to a regular school or otherwise to special education. For professional education and university, however, this does not exist, which may make the transition from secondary education towards professional education more difficult. Therefore extra attention and planning could help to smoothen the transition.
Elizabeth Vroom, DDS, discussed dental issues in DMD. Changes in muscle strength of masticatory and perioral muscles in combination with the development of a large (pseudo) hypertrophic tongue cause changes in the dentition. The shape of the dental arches changes over time including overexpansion of the lower arch. Crossbites and frontal and lateral open bites develop subsequently causing a lack of contact points between upper and lower jaw which makes chewing even more difficult. Dental hygiene is poor in DMD, instructions for caregivers could help overcome certain challenges. Extra attention should be given, for more reasons than only dental, to healthy nutrition. Sugar rich food should be avoided (especially in combination with a low pH as seen in yoghurt and soft drinks). Rinsing and drinking water after every meal is recommended.
Dr Ruben Hendriksen (Maastricht University Medical Center) discussed the prevalence of epilepsy in DMD. Even though it is much less frequent than ADHD and autism, epilepsy is far more common among Duchenne patients (6% vs 0.5-1% in the general population). There are several possible mechanisms and probably also here the Dp71 form of dystrophin plays a role, just like with ADHD and autism (see above).
To improve and implement the standards of care the Duchenne Centre the Netherlands has been established in the Netherlands, which is a collaboration several UMCs and clinics.
The ‘Groei-wijzer’ (growth guide; Marion van Ool, Kempenhaeghe) is a Dutch tool that is used among others revalidation and epilepsy as an aid for parents and professionals to guide children towards independency. It involves questionnaires for children and parents that thereafter will be discussed with a professional to determine the aspects important for the child. These guides are also already used for DMD, on voluntary basis, in several places. For more information see www.opeigenbenen.nu(in Dutch).
Duchenne award and closing remarks
At the end of the day the Duchenne award 2018 was awarded to prof dr Jan Verschuuren for his efforts in establishing the Duchenne Centre the Netherlands and leading the Aladin (All against Duchenne in the Netherlands) consortium.
The head of Duchenne Parent Project NL, Elizabeth Vroom, closed the day with the ‘vision for the future’. The DPP will continue to finance research (this year will especially focus on nutrition and DMD), organising meetings, networking and international collaborations. Furthermore they will keep advocating for patients to improve early diagnosis, access to medicines and improvement of care. Also distribution of information for patients/caretakers, professionals and the general public, and sharing of knowledge between for example parents is an important task. DPP is in the process of setting-up a Duchenne data platform where all patients will have their own ‘locker’ with their data. Thereby they will have access to this data and can control themselves for which objectives this may be used. Data sharing is important to advance research, but the platform will also facilitate results being shared with the patient community. A virtual chat-assistant will help patients to keep their data up-to-date. Patients/caretakers that are interested in testing the platform can contact Mirjam Franken of the DPP (firstname.lastname@example.org).