Holm Graessner

Universitätsklinikum Tübingen · Zentrum für Seltene Erkrankungen

Splice modulating antisense oligonucleotides (ASOs) offer treatment options for rare neurological diseases, including those with very rare mutations, where patient-specific, individualized ASOs have to be developed. Inspired by the development of milasen, the 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop p...

Purpose: Within the Solve-RD project (https://solve-rd.eu/), the ERN-ITHACA (European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies) aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "C...

Background: Multisite research networks such as the project "Collaboration on Rare Diseases" connect various hospitals to obtain sufficient data for clinical research. However, data quality (DQ) remains a challenge for the secondary use of data recorded in different health information systems. High levels of DQ as well as appropriate quality asses...

People living with rare diseases (PLWRD) still face huge unmet needs, in part due to the fact that care systems are not sufficiently aligned with their needs and healthcare workforce (HWF) along their care pathways lacks competencies to efficiently tackle rare disease-specific challenges. Level of rare disease knowledge and awareness among the curr...

Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the dia...

Background Since it first started operating in 2017, the European Reference Network for Rare Neurological Diseases (ERN-RND) implemented a multi-channel communication strategy to effectively reach its target audience: healthcare professionals, patients, researchers, industry representatives and the general public. We first created a website contain...

Background Patient journey maps are increasingly used as a tool that enables healthcare providers to refine their service provision to best meet patient needs. We developed a cervical dystonia patient journey map (CDPJM) that describes the holistic patient experience from pre-diagnosis through to long-term treatment. Methods The CDPJM was develope...

Background Since the first European-wide evaluation of dystonia management in 2016, several efforts have been made to improve dystonia-care. One of these was the development of the Dystonia Disease Group as a part of the European Reference Network for Rare Neurological Diseases (ERN-RND) that implemented several initiatives based on the recommendat...

Zusammenfassung Die Verwendung von einheitlichen Datenformaten (Datenstandards) im Gesundheitswesen dient vier Hauptzwecken: 1) dem Datenaustausch, 2) der Integration von Computersystemen und -instrumenten, 3) der Datenspeicherung und -archivierung und 4) der Unterstützung föderierter Datenbanken. Sie sind besonders wichtig für die Erforschung und...

Zusammenfassung Als Seltene Erkrankungen (SE) gelten in der Europäischen Union (EU) Krankheiten, von denen nicht mehr als 5 von 10.000 Menschen betroffen sind. Aufgrund ihrer Seltenheit sind klinische Expertise und qualitätsgesicherte Versorgungsstrukturen rar, die Forschung ist hier im Vergleich zu anderen Krankheiten erschwert. Diese Probleme kön...

As a result of digitization, the importance of data quality (DQ) is increasing more and more, especially in the field of medicine and science. In the research project “Collaboration on Rare Diseases” of the Medical Informatics Initiative (CORD-MI, FKZ 01ZZ1911R), we developed a framework for assisting the quality of data recorded in different healt...

Background: Patients with rare diseases often undergo a diagnostic odyssey that can last many years until the diagnosis is definitively established. To improve the diagnosis and treatment of these patients, the German National Task Force for Patients With Rare Diseases (Nationales Aktionsbündnis für Menschen mit Seltenen Erkrankungen, NAMSE) has r...

Objective: Patients suspected of having a rare (chronic) health condition have often gone a long way within the healthcare system. To date, little is known about the health-related quality of life of this group of patients. The study aims to describe the health-related quality of life and the perceived distress of patients suspected of having a ra...

In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single...

Background and purpose: Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pat...

Background and purpose: 7,000 rare diseases have been identified, most of them are of genetic origin. The diagnosis of a neurogenetic disease is difficult, and management and training programs are not well defined through Europe. To capture and assess care needs, the Neurogenetics Panel of the European Academy of Neurology (EAN) has performed an e...

Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or con...

https://pubmed.ncbi.nlm.nih.gov/34863918/#affiliation-26

Background Patient involvement in research increases the impact of research and the likelihood of adoption in clinical practice. A first step is to know which research themes are important for patients. We distributed a survey on research priorities to ERN-RND members, both patient representatives and healthcare professionals, asking them to priori...

An amendment to this paper has been published and can be accessed via the original article.

Background: Since it first started operating in 2017, the European Reference Network for Rare Neurological Diseases (ERN-RND) implemented a multi-channel communication strategy to effectively reach its target audience: healthcare professionals, patients, researchers, industry representatives and the general public. It first created a website contai...

Antisense oligonucleotide (ASO) therapies present a promising disease-modifying treatment approach for rare neurological diseases (RNDs). However, the current focus is on "more common" RNDs, leaving a large share of RND patients still without prospect of disease-modifying treatments. In response to this gap, n-of-1 ASO treatment approaches are targ...

Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the dia...

Rare diseases (RDs), in Europe defined as affecting fewer than 5 in 10,000 people, are typically serious and often life-threatening chronic diseases [1]. The RD burden remains high, partially attributed to scarce visibility in the healthcare system due to missing availability of appropriate RD classification and documentation.We review two main pro...

With 263-446 million patients affected worldwide, rare diseases are a global health challenge [1]. As early diagnosis and adequate treatment are often difficult, rare diseases require specialized care. In Germany, care for rare disease patients is often provided at specialized centers (“Zentren für Seltene Erkrankungen”), typically located at unive...

Zusammenfassung Eine Erkrankung zählt in der Europäischen Union zu den Seltenen Erkrankungen (SE), wenn diese nicht mehr als 5 von 10.000 Menschen betrifft. Derzeit existiert mit mehr als 6000 SE eine sowohl große als auch heterogene Menge an unterschiedlichen Krankheitsbilder, die in ihrer Symptomatik komplex, vielschichtig und damit im medizinisc...

Establishing a diagnosis in people with a suspected rare disease requires a structured interdisciplinary approach. In some of these cases and in people with an established rare disease but a complex course, expertise from outside the treating center may be helpful or even required to determine the best possible diagnostic or therapeutic plan. To su...

Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of th...

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient’s data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four Europ...

Improved care for people with dystonia presents a number of challenges. Major gaps in knowledge exist with regard to how to optimize the diagnostic process, how to leverage discoveries in pathophysiology into biomarkers, and how to develop an evidence base for current and novel treatments. These challenges are made greater by the realization of the...

European Reference Networks (ERNs) were founded on the principle that many rare disease (RD) issues are pan-European and any single Member State cannot solve them alone. In 2021, ERNs are already in the deployment stage; however, their day-to-day functioning and realization of their potential are still severely hampered by many challenges, includin...

Care pathways (CPW) are used worldwide to structure care processes within the patient-centered care concept. Rare diseases (RD), defined as those affecting less than 5 persons per 10,000 and including up to 10,000 different diseases, present unique challenges to CPW development due to their rarity and a large number of disease entities, chronic and...

While rare diseases (RDs) are by definition of low prevalence, the total number of patients suffering from an RD is high, and the majority of them have neurologic manifestations, involving central, peripheral nerve, and muscle. In 2017, 24 European Reference Networks (ERNs), each focusing on a specific group of rare or low-prevalence complex diseas...

Background: Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of patients waiting 5 to 30 years for one. It is essential to raise awareness of patients and clinicians of existing gene and variant-specif...

Background: Patient involvement in research increases the impact of research and the likelihood of adoption in clinical practice. A first step is to know which research themes are important for patients. We distributed a survey on research priorities to ERN-RND members, both patient representatives and health care professionals, asking them to prio...

Background Diagnosis of rare movement disorders (MD) is difficult and specific management programs are not well defined. Thus, in order to capture and assess care needs, the European Reference Network for Rare Neurological Diseases (ERN‐RND) has performed an explorative care need survey across all European Union (EU) countries. Methods This is a m...

Die 2017 auf der Wartburg in Eisenach gegründete Deutsche Akademie für Seltene Neurologische Erkrankungen (DASNE; dasne.de) ist Wegbereiter für eine optimierte Diagnostik und personalisierte Betreuung und Behandlung von Patienten mit seltenen neurologischen Erkrankungen aller Altersgruppen. Als erste derartige Einrichtung in Deutschland verfolgt di...

Although individually uncommon, rare diseases (RDs) collectively affect 6–8% of the population. The unmet need of the rare disease community was recognized by the European Commission which in 2012 funded three flagship projects, RD-Connect, NeurOmics, and EURenOmics, to help move the field forward with the ambition of advancing -omics research and...

Zusammenfassung Die Deutsche Akademie für Seltene Neurologische Erkrankungen (DASNE) will Wegbereiter für eine optimierte Versorgung von Patienten mit seltenen neurologischen Erkrankungen sein. Als erste Institution in Deutschland verfolgt die Akademie die Bündelung und kontinuierliche Weiterentwicklung von Expertise im Bereich seltener neurologisc...

Zusammenfassung Seltene Erkrankungen sind definitionsgemäß jede für sich selten, aber wegen ihrer großen Zahl in ihrer Gesamtheit häufig. Hierdurch besteht bei Ärzten nur selten Erfahrung für die einzelnen Erkrankungen; gleichzeitig stellt die Erkrankungsgruppe eine häufige Herausforderung dar. Aufgrund der mangelnden Kenntnisse bleiben viele Patie...

Ab dem Jahr 2017 werden in der Europäischen Union Europäische Referenznetzwerke (ERN) für Patienten mit seltenen Erkrankungen etabliert werden. In den ERN wird Expertise in Zentren gebündelt und über Grenzen hinweg ausgetauscht, um den Zugang zur Diagnose und Behandlung zu ermöglichen und zu erleichtern. Die Integration der ERN in die Organisation...

There is growing interest in having objective assessment of health-related outcomes using technology-based devices that provide unbiased measurements which can be used in clinical practice and scientific research. Many studies have investigated the clinical manifestations of Parkinson’s disease using such devices. However, clinimetric properties an...

Introduction: Dyskinesias in Parkinson's disease (PD) patients are a common side effect of long-term dopaminergic therapy and are associated with motor dysfunctions, including gait and balance deficits. Although promising compounds have been developed to treat these symptoms, clinical trials have failed. This failure may, at least partly, be expla...

Background Currently, assessment of symptoms associated with Parkinson’s disease is mainly performed in the clinic. However, these assessments have limitations because they provide only a snapshot of the condition. Methods The feasibility and usability of an objective, continuous and relatively unobtrusive system (SENSE-PARK System), which consist...

Background: Parkinson's disease (PD) is a neurodegenerative disorder with fluctuating symptoms. To aid the development of a system to evaluate people with PD (PwP's) at home (SENSE-PARK system) there was a need to define parameters and tools to be applied in the assessment of 6 domains: gait, bradykinesia/hypokinesia, tremor, sleep, balance and cog...

Background: There is a growing interest in the objective assessment of health related outcomes using technology providing quality measurements to be applied not only in daily clinical practice, but also in scientific research. Differences in the understandings of the condition and the terminology used between people with Parkinson's (PwPs), clinic...

In Germany, many highly specialized facilities for the diagnosis and treatment of rare diseases exist. However it is quite difficult for patients to find the required specialists because of the fact that information on the internet is scattered and of variable quality. The German Federal Ministry of Health initiated several activities to address th...

Zusammenfassung IonNeurONet ist ein vom Bundesministerium für Bildung und Forschung (BMBF) gefördertes Verbundforschungsprojekt der Universitäten Tübingen und Ulm sowie der CeGaT GmbH, Tübingen, mit dem Ziel, die Erkrankungsmechanismen seltener neurologischer und ophthalmologischer Ionenkanalerkrankungen aufzuklären, die als Basis für die Entwicklu...

The INCF Secretariat organized a workshop to focus on the “role of neuroinformatics in the processes of building, evaluating, and using genetic animal models for brain diseases” in Stockholm, December 13–14, 2009. Eight scientists specialized in the fields of neuroinformatics, database, ontologies, and brain disease participated together with two r...

Das bundesweit erste Behandlungs- und Forschungszentrum für Patienten mit seltenen Erkrankungen (SE) ist in Tübingen eröffnet worden. Eine Erkrankung gilt als „selten“, wenn durchschnittlich weniger als 1 von 2000 Personen daran erkrankt ist. In Deutschland leben etwa 3Mio. Patienten mit SE. Bis zu 80% der SE sind nach derzeitigem Kenntnisstand gen...