Author: ERN-RND

Despite considerable achievements in genetics in dystonias, their response to possible treatment such as Deep Brain Stimulation (DBS) remains to be elucidated. Since blinded randomized study protocols are spare, case series and short/long term outcome is of pivotal interest for patients suffering monogenic dystonia.

Therefore, ERN-RND is performing a systematic review to assess the efficacy of DBS as a treatment for monogenic dystonia symptoms. The objective is to develop evidence- and consensus-based management recommendations for the benefit of DBS for patients with monogenic dystonias in a collaborative effort within the network. Get an insight on preliminary results of the review in this video interview with Sylvia Boesch.

Watch the video interview here.

The methodology used for the systematic review is already published. Learn more here.

We are happy to announce that our patient advocate John Gerbild (representative for: Ataxia/HSP) is now a newly elected Board Director at EURORDIS! Congratulations, John! Also, Graham Slater and Kirsten Johnson have been re-elected to their seats.

Find out more about John here. Find all Board Directors here.

Did you miss a session during our winter school Challenges of Treating Rare Neurological Diseases this year? You can now watch the recordings! Please find below a list of the recordings. You can also find them on our website PAST WEBINARS.

Francesca Fumagalli – IRCCS San Raffaele Scientific Institute, Milan, Italy
Treatment of metachromatic leukodystrophies

Caroline Sevin and Fanny Mochel -Kremlin-Bicêtre University Hospital and La Pitié-Salpêtrière Hospital, Paris, France
Leriglitazone trial in adrenoleukodystrophy

Thomas Opladen  – University Children’s Hospital, Heidelberg, Germany
Treatment of Aromatic l-amino acid decarboxylase (AADC) deficiency

Bernhard Landwehrmeyer -University Hospital Ulm, Germany
Disease-modifying treatment approaches/Trials in Huntington disease (HD)

Marlen Lauffer -Leiden University Medical Center​, The Netherlands
Treatment of nano-rare neurological diseases

Annemieke Buizer -Amsterdam UMC, The Netherlands
Treatment of spasticity in children with rare neurological disorders – who, why, when and what?

Ronald Buijsen -Leiden University, The Netherlands
Treatment of ataxia – genetics based

Gabriella Paparella -IRCCS Eugenio Medea, Institute for rehabilitation medicine, Italy
Treatment of ataxia – rehabilitation based

Michèl Willemsen -Radboudumc, Nijmegen, The Netherlands
Introduction – systematics of non-neurological aspects

Mayke Oosterloo -Maastricht University Medical Center, The Netherlands
Cognitive and psychiatric treatment in Huntington’s disease

Adam Vogel – University of Melbourne, Melbourne, Australia
Speech treatment in Ataxias

It takes „about one year from the first symptoms to the first consultation of a physician, and another one year to reach a diagnosis. And then patients with this diagnosis are sent to specialized centres” – which are ERNs.

Our member Robert Rusina is referring to a speech language disorder, known as Primary Progressive Aphasia (PPA), for which diagnosis is often delayed and therapeutic options sparse. So after this long journey is over and patients can be treated – how does clinical practice for PPA in ERN-RND centers look like? 

A survey among ERN-RND centers (physicians, neurologists, psychiatrists), specialized in Frontotemporal Dementia was conducted in order to evaluate current clinical practice with regards to available PPA management options (like referral pathways, proportion subtypes, speech and language therapy).

For a taste of what is to come in the paper, watch our video interview with Robert Rusina here.

Myoclonus-dystonia syndrome (MDS) is a genetic movement disorder with childhood-onset, most frequently caused by SGCE defects. For this survey two different questionnaires were distributed: one among neurologists from ERN-RND, and another among patients and families with SGCE-related MDS.

Offering a multidisciplinary approach that tackles both movement disorders and neuropsychiatric comorbidities could enhance the diagnosis and treatment of patients with SGCE-MDS.

PAPER
Approach to Myoclonus Dystonia Syndrome: A European Reference Network Survey
Vanegas MI, Marcé-Grau A, Cazurro-Gutiérrez A, Hamami F, Timmers ER, Weißbach A, Tijssen MAJ, González V, Miguel LD, Martin M, Benson M, Reinhard C, Pérez-Dueñas B. Approach to Myoclonus Dystonia Syndrome: A European Reference Network Survey. Mov Disord Clin Pract. 2025 Mar 15. doi: 10.1002/mdc3.70028. Epub ahead of print. PMID: 40088059.

MLD is a neurodegenerative disorder, that affects children at a very young age, leading to a premature death. In a pilot program (2021-2023) in which 109,259 newborns were screened for metachromatic leukodystrophy, blood-spot samples were obtained for analysis and three newborns with MLD were identified, which made presymptomatic treatment possible.

“This gene therapy shows a high efficacy, enabling an almost normal cognitive and motor development for the children, if it is applied in the presymptomatic stage of the disease”, says Lucia Laugwitz, MD, from the Paediatric Department at the University Hospital Tübingen. This success shows why it is important to implement MLD in the newborn screening.

Following the publication of this German pilot study, Norway was the first country to implement NGS (Next Generation Sequencing) for MLD on a national level. With hopefully more countries to follow soon.

Watch the video here.

What do centres of expertise gain from participating in an ERN?
Graessner: An immediate advantage is when doctors at such a centre of expertise are not sure of the right diagnosis or treatment, they can refer to the ERN’s multidisciplinary team consultation. Several experts in Europe then meet online to discuss the patient and form a recommendation for the referring centre of expertise. Other benefits include that ERNs maintain registries with data on patients with the relevant conditions, provide training to doctors, and develop guidelines, care standards and clinical decision support tools.

What do patients gain from this?
Graessner: Our slogan is: knowledge travels, not the patient. So in most cases, patients can visit a centre of expertise in their home country and get diagnostics and treatment through that centre, accessing the ERN expertise whenever needed. Another advantage for patients is that ERNs develop so-called patient journeys. These are visual overviews of the disease symptoms and care needs a patient may experience during different stages of the disease. These materials are now available for different disease groups and in several European languages (ERN-RND, EURO-NMD, epiCARE) In this way, patients can quickly and easily obtain knowledge about the disease, which incidentally also applies to family members and non-specialist doctors.

How do you see the near future of ERNs?
Graessner: After a development phase of several years, the ERNs are now to the point where they clearly add value, but there are still some important areas for improvement. The various centres of expertise are connected, but integration into national healthcare systems lags behind, for example when it comes to the national adoption of guidelines and care standards from the ERNs. To improve this integration, a three-year project called JARDIN was launched in early 2024. Another bottleneck is funding. So far, only the centres coordinating the networks, one centre per network, receive funding from the European Commission. Such a reimbursement is also needed for the other centres of excellence in the network, because participating in an ERN is now extra work and that is not sustainable in the long run.

(Excerpt from the interview with Holm Graessner by Moniek Veltman (for de neuroloog). The original article was published in Dutch here.)

“Does current policy meet the needs of the rare neurology community” and “The impact of rare neurological conditions, through the lifecourse”- those were the two panel discussions at EFNA’s meeting “Shaping the Future: Policy Responses to Rare Neurological Challenges” with the MEP Interest Group Brain Health and Neurological Conditions on February 19 in Brussels.

(European) Patient Organizations, represented through Arabela Acalinei, Merete Haaseth Avery, Jean-Philippe Plançon, José Ángel Aibar and Lutgarde Allard, ERN-RND coordinator Holm Gaessner and MEPs Billy Kelleher, Tilly Metz, Tomislav Sokol, Margarita de la Pisa Carrión, Ondřej Dostál and Romana Jerković attended this meeting.

Holm Graessner emphasized the importance of ERNs – on European as well as on national level – and thus the need to sustain them in the future. He also encouraged to make more use of the ERNs, also in regards to research and HTA (Health Technology Assessment) purposes – the MEPs were fully supportive towards those policy asks.

Watch the recorded meeting here.

Within the Solve-RD project, over 300 experts from different European countries and Canada re-analysed genome data from undiagnosed 6447 patients. They were able to diagnose 506 patients and their families. For 15% of the patients, there are leads for actionability, in some including treatment; in other cases, the diagnosis provides clarity for the patients and their families.

Find the press release here.

Learn more in the paper: Laurie, S., Steyaert, W., de Boer, E. et al. Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses. Nat Med (2025). https://www.nature.com/articles/s41591-024-03420-w

Our coordinator Holm Graessner is now commissioner for the freshly launched Rare Diseases International Lancet Commission on Rare Diseases (RDI-LCRD)! We feel really honoured that among the 27 commissioners from all over the world he is the only one coming from an ERN.

The initiative is dedicated to generating evidence- and equity-informed recommendations that are implementable and impactful across all countries to dramatically improve the lives of PLWRD. The RDI-LCRD brings together 27 Commissioners who represent countries from around the world and bring diverse perspectives (gender, lived experience) and expertise (ethics, clinical care, research, biostatistics, economics, regulatory, technology, innovation) from a variety of healthcare systems.  

Find more information here: press release, website, project description  (registration for FREE account required), LinkedIn.

You can now find us on BlueSky: @ern-rnd.bsky.social

Did you know that BlueSky was conceptualized in 2019 by former Twitter CEO Jack Dorsey and developed in parallel with Twitter? This is why it looks and functions pretty similar like twitter. So, moving from X to BlueSky is very easy, as everything is familiar – and it’s even in the same blue as twitter was!

Try it out and follow us to BlueSky. We hope to see you there soon!

Why is a quality assessment on European level important for next generation seuencing (NGS)? What needs to be improved and what’s the benefit of having a network of expert centers like ERN-RND to work with?

Ales Maver, clinical laboratory scientist at the University Medical Center in Ljubljana, talks about the insights and outcomes of the quality assessment for NGS that was done within the ERN-RND network 2024 in this video:

For more Information, see paper:
Quality assurance for next-generation sequencing diagnostics of rare neurological diseases in the European Reference Network.

Aleš Maver, Katja Lohmann, Fran Borovečki, Nicola Wolstenholme, Rachel L. Taylor, Malte Spielmann, Tobias B. Haack, Matthias Gerberding, Borut Peterlin & Holm Graessner

The combination of newborn screening, care pathway and respective therapies led to a major breakthrough for rare diseases in this study: “Newborn Screening and Presymptomatic Treatment of Metachromatic Leukodystrophy”.

The study was conducted in the German expert centers Hannover and Tübigen over the period of nearly 2 years. By using a three-tiered screening strategy 3 of over 100.000 newborn infants were screened positive for MLD and received treatment in accordance with the proposed care pathway. 

Find the whole article here.

Patient Journeys are practical quick overviews that guide you through the stages of a rare neurological disease. But do you know how patient journeys are developed? From the first draft made by a patient advocate over surveys and evaluations by clinicians – a patient journey is a lot of work.

How exactly this development process looks like and which ways of disseminating we are focusing on – listen to EURORDIS new episode of ERNs on Air (episode 6) and find out: https://www.eurordis.org/rare-on-air/

Read now our newly published paper on “Quality assurance for next-generation sequencing diagnostics of rare neurological diseases in the European Reference Network” by Aleš Maver, Katja Lohmann, Fran Borovečki, Nicola Wolstenholme, Rachel L. Taylor, Malte Spielmann, Tobias B. Haack, Matthias Gerberding, Borut Peterlin & Holm Graessner in the European Journal of Human Genomics.

https://www.nature.com/articles/s41431-024-01639-2

Abstract

In the past decade, next-generation sequencing (NGS) has revolutionised genetic diagnostics for rare neurological disorders (RND). However, the lack of standardised technical, interpretative, and reporting standards poses a challenge for ensuring consistent and high-quality diagnostics globally. To address this, the European Reference Network for Rare Neurological Diseases (ERN-RND) collaborated with the European Molecular Genetics Quality Network (EMQN) to establish an external quality assessment scheme for NGS-based diagnostics in RNDs. The scheme, initiated in 2021 with a pilot involving 29 labs and followed by a second round in 2022 with 42 labs, aimed to evaluate the performance of laboratories in genetic testing for RNDs. Each participating lab analysed genetic data from three hypothetical cases, assessing genotyping, interpretation, and clerical accuracy. Despite a majority of labs using exome or genome sequencing, there was considerable variability in gene content, sequencing quality, adherence to standards, and clinical guidance provision. Results showed that while most labs provided correct molecular diagnoses, there was significant variability in reporting technical quality, adherence to interpretation standards, reporting strategies, and clinical commentary. Notably, some labs returned results with the potential for adverse medical outcomes. This underscores the need for further harmonisation, guideline development, and external quality assessment in the evolving landscape of genomic diagnostics for RNDs. Overall, the experience with the scheme highlighted the generally good quality of participating labs but emphasised the imperative for ongoing improvement in data analysis, interpretation, and reporting to enhance patient safety.

“Getting coordinated care is not a pipe-dream. It is a reality in Innsbruck and can be a reality in other places” (Patient Advocate from ERN-RND)

The question our ePAG asked ourselves in January of 2024: What does good care look like? We thought it wise to visit an Expert Center to learn about the expertise and the standards that they provide to patients. We identified a center that covered all of the representative diseases in the ERN-RND. We then decided on the questions we wanted answered.

On 24 May, the ePAG of the ERN-RND left their mark in Innsbruck, where they visited Dr. Sylvia Boesch and her team -at the Center for Rare Movement Disorders Innsbruck (CRMDI) in the Medical University Innsbruck.

Dr. Matthias Amprosi, part of the neurology team at the CRMDI made a presentation, which covered the majority of the questions we sent them prior to our visit. We learned about the clinic and how many patients they see and help per year. We learned about studies that are currently in progress. We learned that there are also organizational, nursing and physiotherapy teams, as well as social workers, all of whom are exclusively assigned to the Department of Neurology. We then saw that in action.

We visited the physiotherapy center where you learn skills while you’re having fun. For example, you can use the h/p/ cosmos fitness trainer for gait analysis while watching a screen in front of you and stepping over objects “in your way.” You can play Wii Fit or, you can use the tyromotion to train fine motor skills by copying a simple drawing.

We also met a 24-year-old male with Friedreich’s Ataxia, who was being advised by his doctors about appropriate jobs because the social welfare office isn’t familiar with that disease and cannot offer advice.

Our ePAG had this to say about the visit: “The presentation of the center’s entry into the ERN was amazing and it was so interesting to see how they work with the ERN network and understand the mutual benefits. It was also interesting to get an overview and to learn about the studies that are in progress at the moment. The implementation of rehabilitation, research and training into the clinical units is impressive. This is a forward-leaning and enthusiastic staff. Also impressive is the holistic approach, in both physiotherapy and in Sylvia’s approach of taking very good care of her patients.”

To thank Dr. Bösch for the visit, the patient representatives gave her a zebra figurine as a symbol of rare diseases: “When one hears hoofbeats, it isn’t necessarily a horse, it can be the much rarer zebra.”

What is equally impressive is how well this ePAG works together. We genuinely like each other and have spent time developing our professional relationship for the benefit of all the people we represent.

Report written by Lori Renna Linton, member of the ERN-RND European Patient Advocacy Group (ePAG)