Yesterday’s announcement by the biotechnology company Trophos SA of the lack of effectiveness of their compound olesoxime adds to the long list of drugs that have failed to live up to their early promise in the lab.
It’s a story that’s common across the world of neurodegenerative disease, including common conditions such as Parkinson’s disease and Alzheimer’s disease. The path from bench to bedside is fraught with pitfalls….
In their press release, Trophos suggested that trials have to be conducted when the ‘window of opportunity’ is greatest – the sooner a drug is administered the better its effect is likely to be. Otherwise, we don’t know whether these treatments genuinely do not work or is it simply a case of ‘too little, too late’?
Certainly, companies such as Biogen Idec have picked up on this, restricting the time limit for inclusion in their trial of dexpramipexole to two years from symptom onset, as opposed to the three year (and sometime longer) limit that has been used in previous trials. It means that Biogen Idec has to involve more local MND clinics to recruit the numbers needed, for the trial, which increases the cost, but they view this as necessary if they are to increase the chances of a positive result.
Similarly, the way MND manifests and progresses can be so different in one individual compared to the next, meaning that trials need to recruit large numbers of participants to reduce the statistical ‘noise’ – once again increasing the already high cost and complexity of the trial.
We will only make major inroads into earlier diagnosis and more accurate predictions of how the disease will progress if we can identify biomarkers – specific biochemical and/or structural changes that occur within the brain and spinal cord that provide us with a unique ‘fingerprint’ of MND.
Biomarkers can also be tailored to look at the effects of specific drugs in trials. Even if it is unclear whether a drug is working on the ‘outside’ (on muscle function for example) it would at least be possible to confirm it was working on the ‘inside’ by reaching the right parts of the brain and spine and acting on the correct chemical processes.
In a nutshell, biomarkers would likely lead to smaller, faster and more accurate trials. That would mean trials could be performed more cheaply – and cheaper trials would almost certainly mean more trials.
This is why the MND Association sees biomarker research as so important. We are currently supporting three clinical biomarker projects (in London, Oxford and Sheffield) which are among the most comprehensive examples of this research in the world. Without the commitment and enthusiasm of those who participate, we wouldn’t be able to create these vital research resources which, as highlighted in previous postings, are beginning to generate promising early results.
But these projects are just the start. Their findings will need to be confirmed in much larger studies, involving the collaboration of MND clinics across many countries, collecting clinical data and samples to precise scientific protocols. This was the rationale behind a major biomarker funding initiative announced earlier this year under the European Union Joint Programme in Neurodegenerative Diseases (JPND). Established by 23 European countries, the JPND Research Call invited funding bids to assist the harmonisation of biomarker collections and the development of new methods of analysing the samples.
On Friday, JPND announced the four projects shortlisted on the basis of “scientific excellence” for a share of the €15 million (approx £12.6 million) research fund. One of these projects is SOPHIA (Sampling and biomarker OPtimisation and Harmonisation In ALS).
Co-ordinated by Prof Leonard van den Berg, the SOPHIA initiative will span up to 16 centres across 12 European countries, including the MND Association’s Sheffield and Oxford Care Centres. The precise level of funding has not yet been determined, but nonetheless this provides a fantastic platform on which major international biomarker research can be developed. We will of course keep you posted once the final outcome is known.