This article was written by Nicola Waters and Lee Millard and originally appeared on the United2EndMND website: https://united2endmnd.org/2024/02/19/behind-the-scenes-of-experts-als/

EXPERTS-ALS is an innovative new platform, which will ‘screen’ (not trial) drugs and compounds to find the ones most likely to be successful at a full phase 3 trial. It will do this by ‘quickly’ looking at the most promising prognostic biomarker, Neurofilament Light Chain (NFL). It is the first major patient facing project of the new UK MND Research Institute. At the MND/ALS Symposium in Basel in December the project received a lot of interest globally, especially from industry and academics, who were interested in how they could collaborate to screen their drugs.

The logistics of managing this platform are actually pretty staggering, though we don’t really see this as individual participants. 11 centres across the UK* will take part, aiming at a minimum of 165 participants initially, which will increase as new drugs are added.

For each participant, a participating centre will need to do the following:

– A comprehensive assessment at the outset.  This includes a full medical history and a wide range of tests to check if it is appropriate for someone to be part of the screening platform – an absolute priority of the team will be ensuring safety.

– At regular 4 week appointments, there will be bio-samples taken, which will be used in this screening but also in other research.  The NFL biomarker will be tested at the outset and at subsequent appointments.

– Throughout the screening, side effects and safety will be monitored along with how MND/ALS is progressing.

– A final assessment takes place at 24 weeks, where nearly all of the assessments done at the start are repeated.

Each centre needs to organise the logistics of these appointments for multiple patients, with the correct equipment and paperwork – a formidable task!  At all of these appointments, everything needs to be done meticulously and to be recorded precisely, with drugs handled properly – not doing so may mean that adverse effects are missed or worse still the screening ultimately rendered void.

The sheer complexity of the project, including the regular collection of blood samples, has never been attempted at this scale or level of coordination before. The NFL measurements require a brand new and robust infrastructure commissioned to WHO GCLP standards (Good Clinical Laboratory Practice). This is no mean feat and will set the standard globally.

The scientists and analysts at the centre of the screening platform, at Oxford and Sheffield, will be very busy. One of the key innovations is results coming into Oxford regularly, with NFL levels fed into the supercomputer model. Exciting new technology has been acquired through an NIHR grant to analyse samples for biomarkers (see photo above). This dynamic approach will mean that the scientists will be able to know if a drug / compound is potentially a viable trial candidate, or not, much more quickly – for participants, this might even mean a drug candidate arm coming to an end more quickly, allowing new ones to start up.

The central team also need to take account of any adverse events and if necessary, act on the results. Biological samples also all need to be stored so that they can be used for future research. As the screening progresses, with patients joining and leaving, and drug arms starting and ending, the complexity increases.

EXPERT-ALS is hoping to start recruiting in summer 2024. The team will shortly be submitting the final package to the MHRA, ethics and HRA for approval (under the Government’s new joint process to speed up approvals) – another level of complexity. We have been fortunate to be the patient representatives on the project participating in many meetings, reviewing text and giving feedback. We have been so impressed by the commitment and drive of the EXPERTS-ALS team.

So as we all wait for EXPERTS-ALS to start and deliver results, we need to remember the huge amount of work going on behind the scenes. Do spare a thought for the research nurses (the unsung heroes of all clinical trials in our opinion!) trying to organise all the appointments and paperwork!

What next? How will/might I apply to take part in this screening platform? The platform is not recruiting yet but the MND Association trials page and the MND Clinical Studies Group (CSG) Trials page will be updated. And of course, watch this space and website. We will post again on the screening platform as it progresses.

 

*Sheffield, Oxford, Salford, University College London, Newcastle, Cambridge, Edinburgh, Exeter, Liverpool, Cardiff and King’s College (London). For more details see the EXPERTS-ALS team webpage.