About the PROSPAX project
The PROSPAX consortium of patient groups, researchers and clinicians across Europe and Canada (including the UK), set up the PROSPAX project to study the progression of spastic ataxias over time, in a rigorous and harmonised way – from the clinical to the molecular level. This has included clinical, imaging, digital-motor and molecular markers of progression and animal models. As the numbers of people with these specific ataxias are quite low, this harmonisation across countries is necessary to gather enough information about the conditions, helping to prepare for clinical treatment trials. This is called ‘trial-readiness’ and is extremely important for rare conditions.
Ataxia UK has been involved in the project throughout, together with the German ataxia charity The German Heredo Ataxia Society (DHAG) as representatives of the European membership organisation of ataxia patient groups, Euro-ataxia. Ataxia UK also awarded a small grant to Dr Rita Horvath at the University of Cambridge, to support participation through a study site in the UK. Dr Rita Horvarth reflected on the project,
“Our clinical research centre called “MitoCamb” participated as the only UK recruitment site in the large international EU funded PROSPAX consortium over the past 5 years, supported by Ataxia UK. Our Cambridge team recruited and followed up 12 patients and all patients completed the study. The data collected in the UK patients is currently being analysed together with data collected internationally.
We would like to thank everybody who participated in the UK study. We hope that this research will improve patient care, leads to better quality clinical trials and will result in long term patient benefit.”
The project involved developing and validating a number of progression markers for spastic ataxias over time, including clinician-reported outcomes, patient reported outcomes, digital sensor-based, brain imaging and molecular markers. Long-term assessment of a range of outcomes in one uniform cohort has allowed the study of their relationship to each other and their change across all disease stages. This will aid the design of future clinical trials that are optimised for the respective disease stage.
The PROSPAX project, which ran from 2020 to 2024, coordinated a comprehensive study on the disease progression of the two spastic ataxias, Spastic Paraplegia Type-7 (SPG7) and Autosomal Recessive Spinocerebellar Ataxia of Charlevoix-Saguenay (ARSACS). Spastic ataxias represent a rapidly growing group of >100 rare neurodegenerative genetic diseases (prevalence 10 – 15 people in every 100,000) affecting both the cerebellum and corticospinal tract.
Overview of data collected
The project engaged 331 study subjects over 890 visits. A total of 2877 biosamples were collected, enabling a broad spectrum of biomarker and genetic analyses. To read an overview of the data collected in the study, click here to read the PROSPAX infographic.
The PROSPAX project recruited a panel of patient partners to advise on the project. This was a small group of people with ataxia or Hereditary Spastic Paraplegia (HSP) who gave input to the project, to ensure that the patient voice was included in all stages of the project. This is important to us and to Euro-ataxia, as is laid out in the Euro-ataxia patient charter here. The PROSPAX team would like to thank everyone who completed their two surveys on the symptoms experienced by people with ataxia and HSP. The surveys were distributed by ataxia patient groups in seven different countries. There were an amazing number of responses for both surveys, with 1125 responses for Survey 1 and 817 responses for Survey 2! The team have produced a poster about the surveys.
Major results
The study also generated an extensive longitudinal (3 visit) transatlantic multicentre, multimodal progression dataset of clinical, digital-motor, brain imaging, and molecular progression markers in >330 subjects assessed, enhancing multimodal understanding of disease progression, including specific domains like motor function or brain structure. Furthermore, a specialised application, the SPAX app, was developed to assist in the efficient collection and analysis of long-term home-based patient data. You can read more about the SPAX app in an interview with Ilse Willemse, who is responsible for setting up all of the visits for the PROSPAX project and collecting all the data, the on our website here.
The consortium also compiled a new clinical assessment scale, the Spastic Ataxia Composite scale (SPAXCOM). SPAXCOM shows strong correlations with disease stage and duration and improved sensitivity, especially in intermediate disease stages.
Moreover, as a major outcome in parallel to the large-scale multimodal natural history and outcome results at the core of PROSPAX, a key genetic outcome was the identification of six new genes causing spastic ataxias. These genetic advances now facilitate the development of targeted molecular therapies and pave the way towards a precision medicine approach of spastic ataxias.
Altogether, the large-scale efforts of the PROSPAX consortium pioneered a trial-readiness pathway for the large group of spastic ataxias (>100 ataxia diseases) by showcase of ARSACS and SPG7, resulting in so far 44 publications; with many more publications just to come in the next months and years.
This project was funded by the European Joint Programme for Rare Diseases (EJPRD). This project unites PIs from all major European ataxia and spastic paraplegia networks: PREPARE, SPATAX, TreatHSP, Alliance for Treatment in HSP and PLS, ERN-RND and SOLVE-RD as well as top PIs from North America and three ataxia and HSP patient organisations to overcome the limitations of current spastic ataxia research.
