On 22nd and 23rd June 2023, the PROSPAX consortia held their annual meeting at the Rahmi M. Koç Museum in Istanbul, Turkey. The PROSPAX project aims to study the progression of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Spastic Paraplegia 7 (SPG7) over time; from the molecular to the clinical level, including brain imaging, markers of progression and animal models. The meeting was attended by a variety of people across the PROSPAX network, including researchers, clinicians, people with ataxia and the patient advocacy organisation Euro-ataxia. The aim of this meeting was for the PROSPAX consortium to present and discuss the results that they have generated so far.
On Day 1 of the meeting, the results from the PROSPAX natural history study were presented. A natural history study measures a condition over time. The aim of the PROSPAX natural history study is to look at the progression of ARSACS and SPG7 over a 2-year period, to further understand these conditions and to help with future clinical trial planning. Many people with ARSACS and SPG7 have taken part in this natural history study across both Europe and Canada, with 106 people with ARSACS, 138 people with SPG7, and 66 people without these conditions, being involved in the study. It is important to include people without the conditions as ‘control subjects’ to compare to people with ARSACS or SPG7. Results were presented on clinical measures of the conditions as well as data from wearable sensors which provide a vast amount of information on movement. The results from the natural history study will be of important use to plan future treatment trials using these outcomes and for these diseases. Without such natural history data, any efficient planning or design of future treatment trials would literally be impossible. Moreover, these natural history progression data are already being used by the consortium to create a scale containing the best measurements to detect progression in these conditions.
There was also an update on the development of a new assessment tool to measure patient reported outcomes in ataxia and hereditary spastic paraplegia (HSP). Patient reported outcomes are reported directly by the person with the condition rather than the clinician. This is important to look at to ensure that any potential future treatments are meaningful for people with the condition. The results of two large surveys of people with ataxia or HSP from across the world have been used to identify symptoms which are frequent and impactful (more information on the surveys here). These are now being used to develop a questionnaire to assess the conditions over time from a patients’ own perspective.
In addition, there was update on the development of an app designed to assess ARSACS and SPG7 at home. The app uses a smartphone to assess gait, stance, finger tapping, movement and speech. The app has been tested and optimised in both a lab study and a 4-week at-home study, and is now being tested in a longer 8-week study, where the app will be used at the beginning and end of the day. This might allow in the future to assess a patients’ motor abilities remotely at home over time -rather than just single snapshots in a lab or a clinic.
On Day 2 of the meeting, results from MRI brain imaging were presented. This included data from from MRI scans that were taken at the PROSPAX clinical sites prior to the PROSPAX study starting, as well as results from the MRI scans which have been carried out during the PROSPAX natural history study. Results were also presented from a study looking at biological markers of SPG7 in a mouse model of the condition. In addition, Day 2 included data on the different genetic variants present in people with spastic ataxias. Here a test was presented which uses skin cells from people with ARSACS and examines them in the laboratory. The main aim is to have an test at hand which allows to clarify whether a certain genetic variant in the ARSACS gene is pathogenic or not- and thus to provide a patient who might have been uncertain about the diagnosis – with a clear diagnosis. Moreover, this test helps to clarify more detail the function of different mutations in people with ARSACS. This will help us to further understand the mechanisms underlying this condition.
Overall, this meeting was a great opportunity for the PROSPAX consortia to meet, discuss their results and generate new ideas to drive forward research on ARSACS and SPG7.