I hope the slightly provocative little title caught your eye. This is my latest post in my The Devil is the Detail series. I try to sketch out the landscape of drug repurposing in our disease. My aim is to prompt questions and discussion on this important topic.

I have also deliberately made it a warts and all review.

I will be totally upfront. I firmly believe repurposing is a path that must be seriously explored despite the challenges, here, presented. But make no mistake, I will most definitely expose those hairy warts!

We often hear comments from patients and their families vocally critical of research with repurposed drugs and requesting more novel MND specific drug trials.


Repurposing is a research avenue that has gained significant traction over the last few years across many different diseases. Why has it become, or appear to have become, controversial in ours?

I believe that surely our community, truly in their ‘heart of hearts’, just want drug efficacy? Do we really care if a drug is novel or repurposed?

We all seek treatments to bring significant advantage to life along with a good safety profile. Perhaps that word, significant, is key here? I will touch back on this towards the end of this post.

We also absolutely want the most tailored, targeted, and personalised treatments. Nonetheless, we have to acknowledge that the processes to achieve them could take some considerable time. We must be brutally honest with ourselves. This is time which many will not have.

It is a sad, gut wrenching indisputable fact. If diagnosed today, there is no available treatment, even waiting in the wings, likely to halt the unrelenting progression for the majority. This is stark but the same is also true for many other diseases including brain, bowel and pancreatic cancer.

Before I get into the weeds of repurposing a quick diversion into current research.

Novel drugs are vitally important and often the primary and obvious choice. For example, the burgeoning world that involves genetic approaches.

For our disease, the potential for crafting such beneficial treatments is exciting.

The first truly effective drug for our disease is tofersen. It was specifically designed to change the protein produced by the gene SOD1. Mutations in this gene account for about 2% of all disease cases. This drug is now firmly on the map. I don’t use the word lightly, but it was a real breakthrough.

Critically, future genetic based therapeutics may not only be for inherited or causative gene MND cases. Why?

Has tofersen taught research a huge lesson? That deep understanding of the disease is key to major advances?


Our genes contain the instructions for creating proteins and other molecules. These slide around our bodies, performing the jobs that evolution has bestowed upon them.

Altering these products could equally help or harm us. There are now some exciting early genetic investigations with the protein TDP-43. Misplaced clumps of this protein are the pathological sign in the majority of cases of our disease.

There are early studies with TDP-43 protein implicated associated genes. For example UNC13A and STMN2. These experiments might bring help to sporadic cases of MND/ALS. Much like the research that led to tofersen, the knowledge around TDP-43 is growing. It helps formulate sharpened targets and developing drug candidates.

Human genetics is complex. Massive computer power is now helping scientists. They are using it to unravel the secrets of the 3 billion base pairs in our genome. New discoveries, like the emergence and importance of the transcriptome, have appeared. More on this in my next post.

Other avenues of cutting edge research include immunological targets and energy metabolism, to name but two.

Such endeavours are not simple tasks. Above all, they are not quick. Studies can easily take several years before even making to a human safety test, let alone efficacy testing. Genetic treatments persist, despite their powerful media and public perception as a wonder, like all drugs, vulnerable to safety issues.

Just this July, the FDA forced Sarepta to stop using their viral vector gene therapy for specific forms of Muscular Dystrophy. This action was due to 3 deaths from major liver failure.

This is the primary guiding principle that is often (but understandably?) overlooked by our desperate community. Safety must always be at the forefront.

Additionally to genetic approaches, there are monoclonal antibody candidates in the pipeline. These candidates have typically brought a greater risk in disease studies than traditional trials.

What should be done in the meantime as these new, perhaps ultimately more effective, candidates come to the fore?

This is where repurposing could be very valuable indeed.

Repurposing is far more than just simply taking an easy choice.


For well over a century, researchers and pharmaceutical companies have been formulating drugs and compounds. This activity really intensified in the industrial era of the last 70 years.

There are estimates of many millions of catalogued items within pharma libraries and registries. Along the way, many have been trialed. Some have failed, paused, or just shelved.

Amongst these is a class of repurposed, often referred to as repositioned. A repositioned drug candidate is one developed with early safety testing for a specific disease. Nonetheless, it has failed to show any effect for the disease originally being tested or any other disease as yet.

Right now, in 2025, there are quite a few such orphan drugs in this space for our disease.

The potential time (and financial) savings are alluring. Safety is often already established. Nevertheless, if a drug were to be used continuously in a new purpose, there could be wider safety concerns. This could be very applicable for say repurposed antibiotics, which are only typically used for a very limited time.

One often overlooked challenge that arises with a potential future cocktails of drugs is the cumulative sum of side effects. There is a balance of identifying the most potent disease drugs so as to reduce harm. We certainly don’t want 20 drugs to take. Imagine the size of the pill boxes, for goodness sake?!

At a fundamental level, the possibility that a drug could find a new use is, to many, medically intuitive. Why?

Diseases often have common pathways and pathologies. This is becoming more obvious with advances in knowledge, even in seemingly completely unrelated diseases.

For example, cancers and neurodegenerative diseases both show

  • shared molecular pathways including cell cycle regulation, DNA damage and protein control.
  • inflammation and immune dysregulation.
  • energy (Mitochondrial) dysfunction and oxidative stress.

There is therefore good scientific rationale why investigating repurposed drugs might reveal an effective drug for our disease.


This is not only hinted at from examinations of the diseases in isolation. Before even a disease shows itself with symptoms, evidence is growing that there are commonalities.

For example, a mutation in a single gene might lead to drastically different damage to our bodies. This is known as pleiotropy. There are many examples in human disease. I will mention one very relevant but perhaps slightly extreme example?

Schizophrenia and MND/ALS might have shared genetic roots. Small differences in a particular gene’s expression might occur in different parts of the body.

The very real implication is that Neurology and Psychiatry may be very close siblings rather than different families of medicine.

On-target properties of one disease’s effective drug just might thus have significant beneficial effects on another disease. Off-target properties, almost serendipitous, could also be helpful, as we have seen with other repurposing of drugs.

There are many examples of effective drug reuse now. Here are some interesting drugs and programs. This won’t fully do justice to the topic but I hope you find just this small sample intriguing.

  • Avastin – a cancer drug now off-labeled* extensively for macular degeneration in the UK.
  • AZT – a well and truly shelved cancer drug (right at the back of the dusty storage area!) from the 1960s repositioned in the 1990s for the HIV pandemic and still used today. Approved globally for HIV.
  • Tocilizumab is a rheumatoid arthritis drug. It was used during the COVID-19 pandemic for severe pneumonia. The FDA has approved for repurposing. It is also approved for emergency covid-19 use in the UK.
  • Mounjaro (tirzepatide) – Approved for its original use as a diabetic drug. It is now globally in the news for obesity management and widely approved.
  • Thalidomide – This drug has a tragic history for its original purpose. But, the FDA and the UK later approved it for use in several cancers. It has since become a foundational treatment.

I will just add a few more that are under investigation for potential repurposing.

  • Aspirin – a pain management drug long approved for in the UK for heart attack and stroke reduction. Now, in 2025, it is showing early potential in cancer treatment.
  • Metformin – diabetic drug highlighted from the Stampede project for prostate cancer – again with early hints of potential efficacy.
  • Several drugs under early investigation from the Octopus trial platform (akin to EXPERTS-ALS) for MS.


* Off-labeling is one of the ways a drug can be repurposed/reused without formal regulatory approval. It is effectively a decision, by a clinician, to prescribe a drug for a different purpose than any approved use. There are many obstacles to off-labeling, including clinician liability. Nonetheless, Avastin, is an excellent example of its well accepted use. Long standing clinical evidence in day to day use influenced its prevalence. Additionally, commercial cost drivers have made Avastin a defacto commonly used prescribed drug for an unapproved use.

There are recurring themes of shared molecular pathways. Cardiac, viral disease, cancer, and bone disease drugs have all found new uses.

The harsh reality of MND research is quite chilling. There is still an absence of a fully understood and unified disease pathology. Put in other words, science yet has very little insight into exactly how our disease starts and perpetuates.

Perhaps even worse, scientists do not understand the contribution of identified pathways to the disease. So although trials might target several pathways at once, and they have, the disease progression might not sway one bit.

Does this reality also beg as much safe use of existing drugs that come with solid and compelling evidence/plausibility?

Ok enough of the positives!

But very real challenges exist with repurposing drugs. It’s not all sweetness and light. I can hear you saying “show me those warts!”


I now will try and give my view of why the concept is fraught with negativity.

Although there are many examples of success in many diseases there have been serious difficulties, including in our disease.

Right from start of a researcher’s possible investigation into repurposing candidates, gaining the financial investment can be extremely problematic. Money is a real problem.

Patents, for example, can then hold up investigations or even stop them dead in their tracks. But like any challenge, in this imperfect world, there are both solutions and ways to gee it along. For example, academics can seek funding to investigate an existing drug’s prospects. They might do this through government grants or other interested party funding.

One accelerant of the negativity I can see is the sheer number of drug failures in MND/ALS trials. Many of these have been repurposed candidates.

Add to the this the trialing of unique combinations of 2 or more existing compounds. Might the cynical perceive such ‘combos’ as merely a commercial (patent) ploy?

When we add the number of failures to my pet topic, the misuse of statistics, the situation becomes even more murky. It is no surprise that our community feels quite miffed!

And it gets even worse folks, oh yes..

Quite possibly biggest bugbear with repurposed drugs is their potential to take a long time to fail. Actually, this issue applies to any drug, but it just feels more painful if repurposed?

This time to fail is possibly at the centre of our community’s fear. It’s rather ironic, don’t you think, given the rhetoric around extolling repurposing is often about speed?

There are far too many examples, in our disease, of the failure of repurposed drugs. Patients and their families can lose faith in scientists.


Just one such distressing drug failure in our disease was Relyviro. Initially approved by the FDA but then withdrawn after failing a phase III. Relyviro was a prime example of over-egged data. And although the Mirocals consortium study into low dose Interleukin 2 hasn’t failed as such yet, there are complications.

The first trial commenced in 2015. It was not then until May 2025 that the highly anticipated Phase II revealed ambiguous results. The earlier hints of optimism were not realised. To top it all, the peer reviewed paper contained that dreaded phrase all patients and families fear…

“..requires further investigation”.

Putting on the sturdy hat of ‘realism’, this probably now means 5 more years of waiting! This would be for possibly only a modest effect drug and only then if it is finally confirmed as effective. That would be 15 years for a repurposed drug!

One of the leading proponents and supporters of repurposing in MND/ALS is LifeArc. At their MND research conference in March of this year, novel development and repurposing were covered. They shared equal space on the agenda. Both the good and the bad were heavily discussed. Have a watch of some of the sessions on the LifeArc YouTube channel. You can also read United2EndMND’s report on the day.

Clearly there are challenges! I certainly can’t sugar coat the opportunities.

Where does this leave us?


Earlier, in this piece, I touched on significant effect on our disease. What does it mean? How is this defined? Is it perhaps time to take stock? Some questions come to my mind and I suspect readers will have many more.

  • Are we perhaps moving towards an era where the marginal or modest drug might not be invested in?
  • Should our scientists in 2025 be searching for effects on a different scale from those sought in 1994? Back then, research really was in its infancy.
  • Was any drug then, with even relatively small effects, considered a success?
  • Should our researchers align consensus towards more truly effective drugs?

My opinion, and answer to all these questions, is yes. But I acknowledge that this may not be popular. One thing is certain…

I for one don’t want patients to spend valuable time in long trials that might not bring a great deal. I also don’t want those who will be diagnosed in the future to face this same situation. I may have used the wrong words there guys but I hope you get my drift.

How can known pitfalls be avoided and how can the search for effective repurposed drugs be accelerated?


One action any patient, patient family member or friend can consider is to join in a trial or study. They can do this in a role known as Patient and Public Involvement and Engagement (PPIE), not as a patient.

Most studies now mandate such involvement. This helps to keep our scientists and charities focused on the journey. It could help them prioritise long-term goals over the direct road in front of them.

I am now a patient representative in a study and I find it very rewarding. I really believe that we can make a difference. We can flag issues as we see them. It is a real opportunity to express what is valuable to patients. We can convey what is beneficial by getting closer to researchers.

Another way to move ahead is to fail much much quicker as I touched on earlier. This is the prima-facia ambition of EXPERTS-ALS. It is the new screening platform of the UK MND Research Institute. The platform is designed for both repurposed and novel drugs. Take a read of the project website and/or the UK MND Research Institute site.

That’s it for today, and I certainly did deviate from repurposing but for very good reason. Once we start to dig into many aspects of MND/ALS research, it soon becomes clear. The devil really is in the detail.

In my next post I will be looking back at last 10 years or so in MND/ALS research. It is both encouraging but at the same time very poignant for me. I was diagnosed over 11 years ago now. Despite having observed major scientific advances, no tangible treatment choice has arrived in time for many of my new friends. These friends I have made along the road.