Research Papers & Collaborations

Findings from the MND Register project will be published here, as well as via a patient newsletter. Results will also be disseminated through scientific publication, conference presentation and patient / carer groups. Only de-identified data will also be disseminated through scientific publication, conference presentation and service user / carer groups.

Research Papers

June 2026

SYN-MND: Privacy-Preserving Synthetic Motor Neuron Disease Patient Data Generation Using Parameter-Efficient Language Models

Yusuf Abdulle, Taiyu Zhu, Mandy Miresmaeili, Emeka Uzochukwu, Francesca Maher, Andrea Biondi, Amber Collingwood, Modupe Aggreh, Julia Ive, Ahmed Al-Khleifat, Elizabeth Gray, Kevin Talbot, Christopher Tomlinson, Zhi Yao ,Honghan Wu, Richard Dobson, Ben Carter, Alfredo Iacoangeli and Ammar Al-Chalabi

View

June 2026

Motor Neuron Disease Register for England, Wales and Northern Ireland: Protocol for a Population Register

Andrea Biondi, Elizabeth Gray, Modupe Aggreh, Edward Jones, Amber Collingwood, Liam Knox, Andrea Bredin, David Setters. Kevin Talbot and Ammar Al-Chalabi

Despite the existence of several regional registries in the United Kingdom, gaps in geographic coverage have limited the ability to produce accurate national estimates of incidence, prevalence, and regional variation for motor neuron disease (MND). To address these challenges, a comprehensive national register encompassing England, Wales, and Northern Ireland was established to support epidemiological studies, health care planning, and clinical research.

View

June 2025

Gender Differences in Clinical Characteristics and Outcomes of ALS/MND Patients: Insights from the UK Motor Neuron Disease Register

Andrea Biondi, Modupe Aggreh, Elizabeth Gray, Amber Collingwood, Kevin Talbot, and Ammar Al Chalabi

View

June 2025

Epidemiological Insights and Survival Analysis from the UK MND Register

Andrea Biondi, Elisabeth Gray, Modupe Aggreh, Amber Collingwood, Kevin Talbot, Ammar Al-Chalabi

View

June 2025

Analysis of ALS Incidence & Prevalence in England, Wales and Northern Ireland

Modupe Aggreh, Andrea Biondi, Elizabeth Gray, Andrea Bredin, Amber Collingwood, Kevin Talbot and Ammar Al-Chalabi

View

September 2020

Motor Neuron Disease Register for England, Wales and Northern Ireland – an analysis of incidence in England

Sarah Opie-Martin, Lynn Ossher, Andrea Bredin, Anna Kulka, Neil Pearce, Kevin Talbot, and Ammar Al-Chalabi

Amyotrophic lateral sclerosis (ALS) has a reported incidence of 1–2/100,000 person-years. It is estimated that there are 5000 people with ALS in the UK at any one time; however, the true figure and geographical distribution, are unknown. In this study, we describe the establishment of a population register for England, Wales, and Northern Ireland and report-estimated incidence. Methods: People with a diagnosis of ALS given by a consultant neurologist and whose postcode of residence is within England, Wales, or Northern Ireland were eligible. The catchment area was based on six data contributors that had been participating since 2016. All centres included in this analysis were in England, and therefore Wales and Northern Ireland are not included in this report. Crude age- and sex-specific incidence rates were estimated using population census records for the relevant postcodes from Office of National Statistics census data. These rates were standardized to the UK population structure using direct standardization. Results: There were 232 people in the database with a date of diagnosis between 2017 and 2018, when missing data were imputed there were an estimated 287–301 people. The denominator population of the catchment area is 7,251,845 according to 2011 UK census data. Age- and sex-adjusted incidence for complete cases was 1.61/100,000 person-years (95% confidence interval 1.58, 1.63), and for imputed datasets was 2.072/100,000 person-years (95% CI 2.072, 2.073). Discussion: We found incidence in this previously unreported area of the UK to be similar to other published estimates. As the MND Register for England, Wales, and Northern Ireland grows we will update incidence estimates and report on further analyses.

View

research papers from collaborators

August 2024

Mapping the natural history of amyotrophic lateral sclerosis: time-to-event analysis of clinical milestones in the pan-European, population-based PRECISION-ALS cohort

Alejandro Caravaca Puchades, Harry E. McDonough, Ammar Al-Chalabi, Adriano Chiò, Philippe Corcia, Miriam Galvin, Orla Hardiman, Mark Heverin, Frederik Hobin, Oskar Holmdahl, Caroline Ingre, Nikita Lamaire, Éanna Mac Domhnaill, Umberto Manera, Robert McFarlane, Mohammed Mouzouri, Fouke Ombelet, Sarah Opie-Martin, Stefan Sennfält, Cristina Terrafeta Pastor, Jan H. Veldink, Philip Van Damme, Leonard van den Berg, Ruben P.A. van Eijk, Rosario Vasta, Daphne N. Weemering, Pamela Shaw, Christopher J. McDermott and Mónica Povedano Panadés

Understanding the ALS disease trajectory and factors influencing the heterogeneous disease course is important to guide clinical care and stratify individuals to effectively assess therapeutics in clinical trials. Population-based datasets from nine European ALS care centers were collated. Time-to-event analysis was conducted for key clinical milestones: symptom onset, diagnosis, gastrostomy insertion, noninvasive ventilation (NIV) initiation, and survival. Independent prognostic factors were determined. 21,820 people with ALS from nine ALS centers were included. Median age of symptom onset was 63.9 years. Median diagnostic delay was 1.0 years, with median survival of 33.7 months from onset. Prognostic factors for survival included age at onset, baseline vital capacity, progression rate, diagnostic delay, site of onset, and C9orf72-positive status. SOD1 variants D91A and G94C had protective prognostic effects in the whole cohort. Median time from diagnosis to gastrostomy insertion in bulbar-onset disease was 2.34 years. Median time from diagnosis to NIV initiation in those diagnosed between 2010 and 2019 was 3.61 years. Significant differences between ALS clinical center cohorts were seen in time to gastrostomy insertion, time to NIV initiation, and in overall survival time. Our analysis of a large, well-defined, population-based European cohort provides detailed insight into the natural history of ALS, highlighting phenotypic and genetic factors affecting time to key clinical milestones. Further study is needed to determine the drivers in observed differences between ALS clinical center cohorts in time to clinical interventions and overall survival.

View

August 2024

Examining changing working status and caregiver assistance in amyotrophic lateral sclerosis (ALS) using large-scale European databases as part of PRECISION-ALS

Harry McDonough, Robert McFarlane, Alejandro Caravaca Puchades, Adriano Chiò, Philippe Corcia, Miriam Galvin, Mark Heverin, Frederik Hobin, Oskar Holmdahl, Caroline Ingre, Nikita Lamaire, Éanna Mac Domhnaill, Umberto Manera, Mohammed Mouzouri, Fouke Ombelet, Sarah Opie-Martin, Mónica Povedano Panadés, Stefan Sennfält, Cristina Terrafeta Pastor, Jan H. Veldink, Philip van Damme, Leonard van Den Berg, Ruben P. A. van Eijk, Rosario Vasta, Daphne N. Weemering, Ammar Al-Chalabi, Pamela Shaw, Christopher J. McDermott and Orla Hardiman

Data from nine specialist European ALS centers and previously funded projects, such as ALSCarE, were collated to examine the working status of people living with ALS (plwALS), the identity of their caregivers, the amount of informal care provided to them, and how these factors change over time. The cohort was stratified into progression groups based on the calculated DFRS and compared longitudinally. Of 21,820 patients identified, 1,184 had working status data, and 237 were followed via semi-structured interview. Within the 1,184 patient group, 45% were in paid employment prior to diagnosis, taking a median of 12 months to leave the workforce post-onset; 83% were no longer working 20 months post-diagnosis. Informal care hours increased over time and were primarily provided by spouses and children, rising from a median of 15.0 hours per week in those less than 12 months from symptom onset to 60.0 hours per week 48–96 months after onset. There was a significant relationship between ALSFRS-R total score and hours of care delivered (r = −0.47, p < 0.001). Up to 45% of plwALS are working prior to diagnosis and their working status changes rapidly, taking an average of 12 months to leave the workforce; caregiver input increases over time, proportional to ALSFRS-R score, with caregivers primarily being spouses and children. Further work is needed to comprehensively capture this information and calculate its true socioeconomic impact.

View

July 2024

Clinical trajectories of genetic variants in ALS: a European observational study within PRECISION-ALS

Robert McFarlane, Sarah Opie-Martin, Alejandro Caravaca Puchades, Adriano Chiò, Philippe Corcia, Miriam Galvin, Mark Heverin, Frederik Hobin, Oskar Holmdahl, Caroline Ingre, Nikita Lamaire, Éanna Mac Domhnaill, Umberto Manera, Christopher J. McDermott, Harry McDonough, Mohammed Mouzouri, Fouke Ombelet, Mónica Povedano Panadés, Stefan Sennfält, Pamela Shaw, Cristina Terrafeta Pastor, Jan H. Veldink, Philip Van Damme, Leonard van den Berg, Ruben P.A. Van Eijk, Rosario Vasta, Daphne N. Weemering, Ammar Al-Chalabi and Orla Hardiman

Nine ALS centers with population-based registries provided data on demographic and disease characteristics — at diagnosis and longitudinally — as part of PRECISION-ALS, to investigate the association between C9orf72, SOD1, FUS, and TARDBP variants on the clinical trajectory of ALS patients in Europe. Of 21,820 ALS patients identified, 9,887 underwent genetic testing for at least one of the four genes of interest: 9.8% carried a hexanucleotide expansion in C9orf72; 2.9% carried a pathogenic variant in SOD1; 1.4% in TARDBP; and 0.8% in FUS. In every case, those with an identified genetic variant presented significantly earlier than those without an identifiable genetic cause, with median age of onset of 59.58 years for C9orf72, 54.19 for SOD1, 58.30 for TARDBP, and 51.16 for FUS, compared with 63.85 years in the variant-negative group. The most frequently identified SOD1 variant was p.D91A, with evidence of other variant clusters in Belgium, Italy, and the United Kingdom.

View

July 2024

Real-world prognostic role of riluzole use in ALS: a multi-center study from PRECISION-ALS

Robert McFarlane, Sarah Opie-Martin, Alejandro Caravaca Puchades, Adriano Chiò, Philippe Corcia, Miriam Galvin, Mark Heverin, Frederik Hobin, Oskar Holmdahl, Caroline Ingre, Nikita Lamaire, Éanna Mac Domhnaill, Umberto Manera, Christopher J. McDermott, Harry McDonough, Mohammed Mouzouri, Fouke Ombelet, Mónica Povedano Panadés, Stefan Sennfält, Pamela Shaw, Cristina Terrafeta Pastor, Jan H. Veldink, Philip Van Damme, Leonard van den Berg, Ruben P.A. Van Eijk, Rosario Vasta, Daphne N. Weemering, Ammar Al-Chalabi and Orla Hardiman

ALS remains an incurable disease with limited treatment options, and riluzole is the most widely available drug. Using data from the PRECISION-ALS database, patients treated with 100 mg of riluzole daily at diagnosis were retrospectively analyzed and compared with those who were not treated. ALSFRS-R slope from onset to diagnosis (ΔFRS) was calculated and used to stratify patients into fast, intermediate, and slow progressors. Overall survival differed significantly between treated and untreated patients (HR 0.70, 95% CI 0.69–0.79), independently of sex, site of onset, age at onset, and diagnostic delay; patients treated with riluzole had a median survival 7 months longer than those who did not receive it (17.6 months vs. 10.7 months; p = 2×10⁻¹⁶). The survival benefit was only evident among fast progressors (HR = 0.50, 95% CI 0.40–0.63). Treatment with riluzole is an independent prognostic factor in ALS, though the extended survival associated with its use appears to be confined to fast-progressing patients.

View

July 2024

Respiratory function, survival, and NIV prevalence over time in ALS – a PRECISION ALS study

Stefan Sennfält, Ammar Al-Chalabi, Alejandro Caravaca Puchades, Adriano Chiò, Philippe Corcia, Miriam Galvin, Orla Hardiman, Mark Heverin, Frederik Hobin, Oskar Holmdahl, Nikita Lamaire, Éanna Mac Domhnaill, Harry McDonough, Umberto Manera, Christopher J. McDermott, Robert McFarlane, Mohammed Mouzouri, Fouke Ombelet, Sarah Opie-Martin, Mónica Povedano Panadés, Pamela Shaw, Cristina Terrafeta Pastor, Philip Van Damme, Leonard van den Berg, Ruben P.A. van Eijk, Rosario Vasta, Jan H. Veldink, Daphne N. Weemering and Caroline Ingre

Respiratory function typically deteriorates as ALS progresses and is associated with shorter survival. This study describes respiratory function and the prevalence of noninvasive ventilation (NIV) along the disease trajectory using prospective data from the PRECISION-ALS project. 3,449 ALS patients from six European population-based cohorts were included; 58.1% had multiple assessments of vital capacity, percent predicted (VC%), and 56% had assessments of the revised ALSFRS-R. In those with a survival time of 1–4 years from diagnosis, median VC% declined from 91–97% at the first assessment to 47–50% at the last assessment six months before death; in those with longitudinal assessments, median VC% declined an average of 24 percentage points per year. There was an increase in respiratory symptoms relative to general functional impairment over time, and VC% was strongly associated with survival. The confirmed prevalence of NIV was approximately 3%, 15%, and 25% in patients with a VC% of >80%, 50–80%, and <50%, respectively. There was a trend of worsening respiratory function over time, and in those with impaired respiratory function, significant variation was observed in the introduction of NIV.

View