For the first week of December I had the pleasure of attending the International Alliance of ALS/MND Associations' Annual Meeting and the 34th International Symposium on ALS/MND, both held in Basel, Switzerland. This is the first in-person International Symposium since Perth in 2019. For this edition of Research Directions, I will provide a summary of the presentations I attended in Basel.
The week started off with bang for me with my election to the Board of the International Alliance of ALS/MND Associations, which is an incredible honour. This appointment means I now get to help the Alliance in its goals to add value to MND/ALS associations through the curation and creation of information and by acting as a global gateway through which Alliance Members, people living with MND and their carers and internal and external stakeholders can connect.
This is very exciting and presents a brilliant opportunity to expand my horizons and bring these experiences to MND Australia. Unfortunately this also means that I will be stepping down from my role as Chair of the Alliance Scientific Advisory Council.
The Alliance meeting always commences with the “March of Faces” which highlights those lost to us during the year. Although incredibly sad, it also serves to underline why we do what we do and the incredible inspiration that people living with MND generates.
We were then treated to two days of presentations on a range of topics from MND organisations around the world.
Highlights from these presentations include:
The Alliance meeting then closed with the usual ALS/MND Connect session. This year we had presentations from Dr Jeanine Heckmann describing her efforts to build an African ALS network, Dr. Tim Miller on the development of Tofersen and Dr Ammar Al-Chalabi on the virtual establishment of the UK MND Research Institute and the Experts-ALS trial that will fast-track early-stage treatments using biomarkers. We then had several Scientific Advisory Council members join Ammar and Jeanine for a spirited and wide ranging discussion responding to questions from the audience.
Following the Alliance meeting, we held the first ever Global Research Directors meeting where we brought together the Research Directors from all the major research funding charities. This included MND Australia, Fight MND, the ALS Association (US), the MND Association (UK), My Name is Doddie, MND Scotland, TargetALS, ALS Canada and ALS TDI.
The aim of this meeting was to identify how we can work together, establish a format to continue to meet going forward, and also identify collaborative opportunities on the global scale. This was an incredibly positive and collaborative group, and with close to $200M of annual research funding in the room, stands to be very influential.
The final part of the week was taken up by the 34th International Symposium on ALS/MND. This is a massive research-focussed meeting with 1300 attendees plus another 300 online, making it easily the largest gathering for MND in the world.
On day one, I chose the all day workshop focussed on “Perspectives on ALS and FTD”. This was a fantastic series of sessions covering a range of topics including phenotypes and neuroimaging, biomarkers, trials and prodromal disease (pre-symptomatic diagnosis), pathology, and models and targets. Highlights included:
Day Two opened with a session on Proteostasis and Proteotoxicity featuring two up and coming Australian researchers, Elise Kellett, who is currently funded by MND Australia, and Dr Stephanie Rayner.
The following session was a series of Clinical Trial updates where we received an analysis of the outcomes from the failed phase 3 COURAGE-ALS trial of reldesemtiv. This had previously been announced but it was good to see the data firsthand. It is still not clear why the trial failed following very promising phase 2 results.
Updates were also received on earlier-stage trials for Pridopidine (failed primary ALSFRS-R endpoint but possible efficacy in bulbar and speech function), colchicine (no positive outcomes), AIT-101 (reduced protein clumping as intended, but too small to show effects on disease progression).
We also heard about the two-year results from the open- label extension of VALOR (tofersen) for people carrying the SOD1 mutation. This showed continued improvement and underlines that this treatment is providing significant benefit for this population.
An analysis of the biomarker data from the MIROCALS study for low does IL2 was also provided. Initial results released several months ago were very positive but we are still waiting for the full data analysis to be released. This presentation focussed on only the biomarkers, which showed the treatment seemed to be having a positive effect and was hitting the expected targets. We continue to wait for the full analysis on disease progression.
Further highlights included a session on developing treatments focussed on TDP-43, the protein disrupted in close to 90% of MND patients. TDP-43 is a very complex target but there are some truly innovative approaches being tested to try and directly target this core protein in MND biology. The session “Clinical Stratification and Endpoints” brilliantly highlighted how we can better measure disease and account for the huge challenge of heterogeneity in MND.
The closing session contained some true highlights of the conference. Matthew Harms from the US gave a great overview of genetic testing in ALS detailing opportunities and challenges. Henk-Jan Westeneng from the Netherlands discussed “Survival for patients with ALS: How close are we to developing a robust personalised prediction model?” showing that as we improve our understanding of the genetics and role of biomarkers, prediction models will continue to develop.
The Drs Ayeez and Shelena Lalji & Family ALS Endowed Award for Innovative Healing is an annual, global prize with the goal of identifying therapies and modalities to regain lost function in people living with ALS that is awarded at the Symposium. A standout moment from the meeting came with the presentation of the Lalji Family Award to Dr Neil Schneider and colleagues for their work on the development of a therapy to target FUS (one of the gene mutations associated with ALS).
This work in people living with FUS ALS has demonstrated slowing and even reversing the disease course of FUS ALS in some people. This is even more remarkable given the usual very aggressive disease course occurring in patients carrying the FUS mutation. The team were accompanied on stage by a patient, Anna Kämpfer, who at one stage was completely immobilised and had a tracheostomy, and is now able to walk up and down stairs and breathe unaided. This was truly inspirational and there were few dry-eyes in the room.