Julian Grosskreutz

• Professor
• University of Lübeck

Background: In amyotrophic lateral sclerosis (ALS), heterogeneity of motor phenotypes is a fundamental hallmark of the disease. Distinct ALS phenotypes were associated with a different progression and survival. Despite its relevance for clinical practice and research, there is no broader consensus on the classification of ALS phenotypes. Methods: A...

Importance Treatment options for amyotrophic lateral sclerosis (ALS) remain suboptimal. Results from a phase 2 study of reldesemtiv in ALS suggested that it may slow disease progression. Objective To assess the effect of reldesemtiv vs placebo on functional outcomes in ALS. Design, Setting, and Participants A Study to Evaluate the Efficacy and Sa...

Background In the Phase 3 MycarinG study (NCT03971422), six once-weekly subcutaneous infusions of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo in patients with acetylcholine receptor or muscle-specific tyrosine kinase autoantibody-positive generalized MG (gMG). Following completion of MycarinG, pati...

Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, characterized by tremendous clinical heterogeneity that necessitates reliable biomarkers for the trajectory of the disease. The potential of phosphorylated Neurofilament-Heavy-chain (pNfH) measured in cerebrospinal fluid (CSF) to mirror disease progressive...

Background Generalized myasthenia gravis (gMG) is a rare, chronic, fluctuating and heterogeneous autoimmune disease requiring lifelong treatment. The Phase 3 MycarinG study demonstrated the efficacy and safety of one 6-week cycle of weekly rozanolixizumab in adult patients with gMG. Open-label extension studies demonstrated consistent symptom impro...

Background Myasthenia gravis (MG) is a chronic autoimmune disease causing fluctuating muscle weakness. The MycarinG study showed that rozanolixizumab, a neonatal Fc receptor inhibitor, provided clinically meaningful improvements in MG outcomes in patients with acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) autoantibody-pos...

In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals: improving costal muscle and joint function, reducing atelectasis through insufflation, and clearing bronchial secretions via exsufflation. Despite its perceived benefits, there is limited s...

The processing and analysis of magnetic resonance images is highly dependent on the quality of the input data, and systematic differences in quality can consequently lead to loss of sensitivity or biased results. However, varying image properties due to different scanners and acquisition protocols, as well as subject-specific image interferences, s...

Extracellular vesicles (EVs) are cell-secreted membranous particles contributing to intercellular communication. Coding and noncoding RNAs can be detected as EV cargo, and RNA-binding proteins (RBPs), such as hnRNPA2B1, have been circumstantially implicated in EV-RNA sorting mechanisms. However, the contribution of competitive RBP–RNA interactions...

Objective: To investigate self-assessment of the amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) using the patient's smartphone and to analyze non-inferiority to clinic assessment. Methods: In an observational study, ALSFRS-R data being remotely collected on a mobile application (App-ALSFRS-R) were compared to ALSFRS-R c...

Background In amyotrophic lateral sclerosis (ALS), neurofilament light chain (NfL) was introduced as a prognostic biomarker. More recently, NfL values can be shared on the patient’s ALS app. Also, the ALS functional rating scale (ALSFRS-R) is an established patient-reported assessment of disease progression. The scale can be obtained during clinic...

Objective: To investigate self assessment of the amyotrophic lateral sclerosis functional rating scale revised (ALSFRSR) using the patients smartphone and to analyze noninferiority to clinic assessment. Methods: In an observational study, ALSFRSR data being remotely collected on a mobile application (AppALSFRSR) were compared to ALSFRSR captured du...

Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, presents challenges in predicting individual disease trajectories due to its heterogeneous nature. This study explores the application of texture analysis on T1-weighted MRI in patients with ALS, stratified by the D50 disease progression model. The D50 model, which offers...

Background Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG. Objectives To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study. Design A randomised, double-blind, placebo-controlled...

Objective Robotic arms are innovative assistive devices for ALS patients with progressive motor deficits of arms and hands. The objective was to explore the patients´ expectations towards a robotic arm system and to assess the actual experiences after the provision of the device. Methods A prospective observational study was conducted at 9 ALS cen...

Introduction Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families...

Objective To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). Methods In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower m...

Amyotrophic lateral sclerosis (ALS) is an incurable, rapidly progressive neurodegenerative disease. During the course of ALS, virtually all skeletal muscles are gradually affected, including the respiratory muscles, and the disease is usually fatal within 2 – 5 years of symptom onset. Unequivocal and conclusive tests for ALS do not exist, its disea...

In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals: improving costal muscle and joint function, reducing atelectasis through insufflation, and clearing bronchial secretions via exsufflation. Despite its perceived benefits, there is limited s...

Tofersen is the first effective and approved therapy for familial ALS caused by pathogenic variants in the SOD1 gene. Following treatment with tofersen, neurofilaments in patients CSF and serum display a faster response than clinical parameters, underlining their importance as a biomarker for treatment response in clinical trials. This evidence led...

The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Des...

Background: In April 2023, the antisense oligonucleotide tofersen was approved by the U.S. Food and Drug Administration (FDA) for treatment of SOD1-amyotrophic lateral sclerosis (ALS), after a decrease of neurofilament light chain (NfL) levels had been demonstrated. Methods: Between 03/2022 and 04/2023, 24 patients with SOD1-ALS from ten German AL...

Background and purpose In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add‐on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. Methods We...

Background Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved tre...

Objective Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA) could be determined by presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters...

Amyotrophic lateral sclerosis (ALS) can result into an incomplete locked in state (iLIS), in which communication depends on eye tracking computer devices. Oculomotor function impairments in ALS have been reported, but there is little research, particularly with respect to patients in iLIS. In the present study, we compared reflexive and executive o...

Objective Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA) could be determined by presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters...

The JCM Topical Collection “Amyotrophic Lateral Sclerosis: Latest Advances and Prospects” started in 2020 and currently includes 11 publications reflecting a broad range of clinical research areas in the ALS field [...]

Objective To assess efficacy and safety of cyclical rozanolixizumab treatment, based on study MG0003 with the open-label extensions (OLEs) MG0004 (NCT04124965) and MG0007 (NCT04650854). Methods MG0004 was an OLE study of ≤52 weekly rozanolixizumab subcutaneous infusions. In MG0007, after an initial cycle, cycles were ‘symptom-driven’, administered...

Introduction: In 2021, the Deutsche Gesellschaft für Neurology published a new guideline on diagnosis and therapy of motor neuron disorders. Motor neuron disorders affect upper motor neurons in the primary motor cortex and/or lower motor neurons in the brain stem and spinal cord. The most frequent motor neuron disease amyotrophic lateral sclerosis...

Therapy of motoneuron diseases entered a new phase with the use of intrathecal antisense oligonucleotide therapies treating patients with specific gene mutations predominantly in the context of familial Amyotrophic lateral sclerosis. With the majority of cases being sporadic we conducted a cohort study to describe the mutational landscape of sporad...

Background: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating autoimmune disease. New treatments for this disease are needed because conventional therapies have limitations, such as side-effects (eg, increased infection risk) or inadequate control of symptoms. Rozanolixizumab is a neonatal Fc receptor blocker that might p...

Objectives: High-intensity physical activity and sports prone to repetitive injuries of the cervical spine and head (when associated with vigorous practice) have been suggested as possible risk factors for amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the relationship between the practice of contact sports (boxing, hockey, foot...

An expansion of the GGGGCC hexanucleotide in the non-coding region of C9orf72 represents the most common cause of familial amyotrophic lateral sclerosis. The objective was to describe and analyse the clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72 mutations in a large population. Between November 2011 and Decemb...

Capturing disease progression in amyotrophic lateral sclerosis (ALS) is challenging and refinement of progression markers is urgently needed. This study introduces new motor unit number index (MUNIX), motor unit size index (MUSIX) and compound muscle action potential (CMAP) parameters called M50, MUSIX200 and CMAP50. M50 and CMAP50 indicate the tim...

Objective: To assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses - in terms of progression, duration, and tracheostomy invasive ventilation (TIV). Methods: A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations wer...

Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with a median survival of 2–5 years. An early diagnosis is essential for providing ALS patients the finest management possible. Studies from different countries report a similar median diagnostic delay of around 12 months, which is still far from desir...

Background The ALS Functional Rating Scale in its revised version (ALSFRS-R) is a disease-specific severity score that reflects motor impairment and functional deterioration in people with amyotrophic lateral sclerosis (ALS). It has been widely applied in both clinical practice and ALS research. However, in Germany, several variants of the scale, e...

Nonadherence to medication is a common issue that goes along with increased morbidity and mortality and immense health care costs. To improve medication adherence and outcome in ill people, their reasons of not taking their prescribed medication must be known. Here a dataset is presented based on the longitudinal observational NeuroGerAd study in a...

Aging is a complex process characterized by several molecular and cellular imbalances. The composition and stability of the neuronal cytoskeleton is essential for the maintenance of homeostasis, especially in long neurites. Using human skin biopsies containing sensory axons from a cohort of healthy individuals, we investigate alterations in cytoske...

The neurophysiological technique motor unit number index (MUNIX) is increasingly used in clinical trials to measure loss of motor units. However, the heterogeneous disease course in amyotrophic lateral sclerosis (ALS) obfuscates robust correlations between clinical status and electrophysiological assessments. To address this heterogeneity, MUNIX wa...

Objective: Remote self-assessment of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) using digital data capture was investigated for its feasibility as an add-on to ALSFRS-R assessments during multidisciplinary clinic visits. Methods: From August 2017 to December 2021, at 12 ALS centers in Germany, an observational stud...

There is a growing demand for reliable biomarkers to monitor disease progression in Amyotrophic Lateral Sclerosis (ALS) that also take the heterogeneity of ALS into account. In this study, we explored the association between Magnetic Resonance Imaging (MRI)-derived measures of cortical thickness (CT) and subcortical grey matter (GM) volume with D50...

Objective Amyotrophic lateral sclerosis (ALS) pathogenesis is still unclear, its course is considerably variable, and prognosis is hard to determine. Despite much research, there is still a lack of easily accessible markers predicting prognosis. We investigated routine blood parameters in ALS patients regarding correlations with disease severity, p...

For both patients with amyotrophic lateral sclerosis (ALS) and their next of kin (NOK), the maintenance of quality of life (QoL) and mental health is particularly important. First studies suggest significant discrepancies between QoL reports by patients and NOK, but little is known for advanced ALS stages. To address this issue, we screened 52 ALS...

Motor-assisted movement exercisers (MME) are devices that assist with physical therapy in domestic settings for people living with ALS. This observational cross-sectional study assesses the subjective experience of the therapy and analyzes users' likelihood of recommending treatment with MME. The study was implemented in ten ALS centers between Feb...

Background: There is a growing demand for the development and evaluation of biomarkers that allow the improvement of clinical disease management and trials in Amyotrophic Lateral Sclerosis (ALS). Ideal biomarkers should be able to represent individual disease covered, independent from disease aggressiveness. The D50 model provides distinct paramete...

Introduction: Motor Unit Number Index (MUNIX) is a reliable and non-invasive neurophysiological technique to reflect functional loss of motor units in amyotrophic lateral sclerosis (ALS). MUNIX is even able to show loss of motor units in pre-symptomatic, non-wasted muscles [1,2]. So, it has been recognized as a promising biomarker in ALS. ALS, as a...

Introduction: Amyotrophic lateral sclerosis (ALS) is a multisystemic, neurodegenerative disease, which is characterized by distal axonopathy and motor neuron loss and thereby leads to muscular weakness and death during 3-5 years after symptom onset due to respiratory failure. Neurofilaments are well-established biomarkers in ALS as they show increa...

Background: The therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the last 4 years but treatment responses differ remarkably between individuals and therapeutic decision-making remains challenging - underlining the persistent need for validated biomarkers. Methods: We applied untargeted proteomic analyses to...

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA). Objective: To assess the feasibility of clinical stu...

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease, and only modest disease-modifying strategies have been established to date. Numerous clinical trials have been conducted in the past years, but have been severely hampered by the wide-ranging heterogeneity of both the biological origins and clinical charact...

Objective: Motor-assisted movement exercisers (MME) enable device-assisted physical therapy delivered in domestic settings. This observational study captures the frequency of MME use, subjective experience of the therapy provided and MME recommendation. Method: The prospective cohort study was implemented at ten ALS centres (02/2019-10/2020) and c...

Importance Intravenous edaravone is approved as a disease-modifying drug for patients with amyotrophic lateral sclerosis (ALS), but evidence for efficacy is limited to short-term beneficial effects shown in the MCI186-ALS19 study in a subpopulation in which efficacy was expected. Objective To evaluate the long-term safety and effectiveness of intr...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 indi...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 indi...

Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS progn...

The pathogenesis of the fatal neurodegenerative condition amyotrophic lateral sclerosis (ALS) remains to be fully understood. Blood–brain barrier damage (BBBD) has been implicated as an exacerbating factor in several neurodegenerative conditions, including ALS. Therefore, this cross-sectional study used the novel D50 progression model to assess the...

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unsatisfactory treatment options. Best management and recruitment into clinical trials requires early diagnosis. However, diagnosis is often delayed. Analysis of the diagnostic pathway and identification of the causes of diagnostic delay are imperative....

Emerging studies corroborate the importance of neuroimaging biomarkers and machine learning to improve diagnostic classification of amyotrophic lateral sclerosis (ALS). While most studies focus on structural data, recent studies assessing functional connectivity between brain regions by linear methods highlight the role of brain function. These stu...

Background There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people wit...

A roundtable convened in July 2020 examined issues concerning respiratory support in amyotrophic lateral sclerosis (ALS), with reference to the potential for an early-phase orally administered medication that might either postpone the introduction of noninvasive ventilation (NIV) and/or enhance the benefits to be gained from it. Attention was also...

Introduction. Neurons with long neurites are physiologically remarkable, as they need to transport newly synthesized proteins and organelles (e.g. mitochondria) from the soma over long distances to the synapses, which is essential for neuronal homeostasis. Via adaptor proteins, which walk on microtubules, organelles find their target place. Next to...

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder. As previous therapeutic trials in ALS have been severely hampered by high inter-individual heterogeneity in clinical phenotype, progression speed and survival, the identification of biomarkers that reliably reflect disease progression represents a priority in current A...

Objective: To study disease characteristics, progression and outcome in a group of motor neuron disease (MND) patients beginning with frontotemporal dementia (FTD) by comparing them with patients with the typical motor-onset. Methods: 849 patients recruited from tertiary centers were studied according to FTD-onset and motor-onset. We studied clinic...

Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative syndrome of the human motor neuron system, for which no effective treatment exists. Variability in the rate of disease progression limits the efficacy of ALS clinical trials, suggesting that developing of better biomarkers for prognosis will facilitate therapeutic progress. Here,...

Neuroinflammation significantly contributes to Amyotrophic Lateral Sclerosis (ALS) pathology. In lieu of this, reports of elevated chitinase levels in ALS are interesting, as they are established surrogate markers of a chronic inflammatory response. While post-mortem studies have indicated glial expression, the cellular sources for these moieties r...

Objective: Investigation of treatment expectations and of the perception of therapy in adult patients with 5q-associated spinal muscular atrophy (5q-SMA) receiving nusinersen. Methods: A prospective, non-interventional observational study of nusinersen treatment in adult 5q-SMA patients was conducted at 9 SMA centers in Germany. The functional s...