Welcome, to my first research opinion post of 2019 on the hunt for an effective treatment for MND.

About time!” I hear you cry.

Calm down, readers. I have been deep in thought and wanted to give you something worth sitting down with a nice cup of coffee to enjoy. This stuff doesn’t write itself, I’ll have you know!

An intriguing title today, if I say so myself! Read on, if you dare.

This post is actually my view/opinion of the yearly MND Symposium recently held in Glasgow, Scotland in December 2018.

The coyness of scientists, well, well, well……

Being coy can affect any one of us, especially those who might be in the public eye, or in an influential position.

No Lee! Not that sort of Coy!

Coy, in the context of this update, implies a ‘reluctance’ to give comment or information for various, mostly commonly, innocent reasons, commercial confidentiality or professional ‘etiquette’.

As a person living with MND, I will attempt to break through, in a polite and gentle way, this coyness, which to the layman and many sufferers can result in confusion, and perhaps even, sadly, distrust in professionals and experts. Yes readers, it’s a onein400 exposé.

So let’s travel back to early December 2018 when over 1200 professionals, including neurologists, researchers, clinicians, healthcare practitioners, representatives from worldwide MND associations and patients met for several days of knowledge exchange and networking.

My wife always called these sort of events, when I attended them in my line of business, as jollies! However, in reality they are highly important conferences, and for scientists involved in the battle against this most stubborn disease, groundbreaking. But why, exactly?

The gathering of specialists from around the globe, face to face, staring into the whites of each other’s eyes, laughing, drinking and eating, results in many things happening.

1) Awareness of the breadth of global research, which for the other 51 weeks, is only in the back of the minds of the attendees. Even the best scientists may not have “clicked” or even been aware of the importance of some research.

2) The bringing together of pharmaceutical companies, academia and clinicians creates a productive environment.

3) The seeds of new ideas actually begin their germination under these perfect conditions. I am not overstating this latter point, and I am certain any number of leading researchers at the event left with a new project or involvement in an impending venture.

But rather than even attempt to summarise the vast entire conference, which would be fruitless, I have decided to talk about the result of a question I submitted to the “Ask the Experts” panel organised at the start of the conference. It was streamed on the Internet live and recorded. What I asked was….

My question is to the whole panel. Firstly, thank you all for choosing to work in the most challenging area of human disease research. My question is how do each of you see the path to an effective therapy moving forward over the next 5 years

I was hoping that this open, but bounded, question would allow some beans to be spilled by the normally coy experts.

If you watch/read no more of this video or post, please watch my question and the,answers. It’s only about 7 minutes long. The link, below, should take you directly to the question, but if it doesn’t just jump to 2h 10 minutes and 50 seconds.

youtube video – acknowledgments to MND Scotland

Now wasn’t that good?

I summarise some of the responses from the experts.

Professor Dame Pamela Shaw was both forthright and confident that several gene therapies will report their trial results, and there was a general opinion that we will start to see effective therapies for a proportion of our community.

The sheer speed of testing drugs was highlighted and in particular in testing on stem cells in the test tube. This is NOT stem cell therapy.  It is the testing on stem cells which have been cultured into Motor neurones and the pre-clinical screening of drugs. As my readers will be aware, I don’t believe stem cell therapy will ever work. Using cultivated stem cells, however, is totally revolutionising the pipeline for clinical human trials. It will  focus/target on drugs that could have a real effect in humans. This is before ever-moving on to human trials, ie remove wastage and speed up the search.

Another revealing statement was the information that pharmaceutical companies and academia are working much more closely. Why is this? Well a lot of companies have existing licenses expiring on their blockbuster drugs. They need new drugs! And if a compound can be found that slows the disease, the market will be big enough for their interest, and a growing one.

Finally, and this was a big subject of discussion at the symposium, the approach to human trials is under much consideration. For essential scientific reasons, trials have only used about 6% of MND patients! There is an intent to try to switch this around and perhaps offer trial participation in trials to the majority. It is important to state, that THIS is not yet possible and needs new techniques to be developed, including some of the realisation of real disease bio-markers. Until these are progressed there will not be any move to trials for all.

However, our MND community should NOT get too obsessed with trial participation.

“What Lee!!!?

I know we all feel like we could add something, or perhaps benefit, but the reality is as long as the trials are happening we are moving. Think about it for a minute……see my point?

To give you a taste of the challenges faced by MND researchers in trials, but to also show the approaches under consideration, a conundrum that is occupying the minds of scientists is:

Is MND a series of different conditions resulting in the same damage to motor neurones or is it a single condition?

This is important as it is influencing the approach to treatments. Multiple treatments might be needed, or a single or less treatments may work if a downstream shared pathology process is identified.

The truth lies probably somewhere in between. This conundrum is directly changing trial design/treatment searches right now.

To end this update, no onein400 research opinion would be complete without at least a comment on some specific drug status/new news section! After my earlier posts, onein400.com/research, I have now realised a running commentary on each and every potential small and marginal drug is probably not of any value to anyone.

The overall rate of progress continues to accelerate with more and more worldwide trials, both pre-clinical and clinical.

I will today mention 2, not for impending reasons or anything, but just 2 that should be lightly monitored.

First is a drug called CU-ATSM. It’s a copper formulation, but it is NOT pure copper. It is a drug currently only  used in cancer tracking. However, after some 15 years of work and experiments, it does appear to hold some disease promise with significant disease-slowing in mice. It is very important to note that the only animal model for human MND that is really relevant is a human. A mouse tells you nothing in reality. The results of the Phase 1 safety and dosage tests, in humans, were published at the symposium. They didn’t really set the ground on fire. That is to be fully expected. It is only Phase 1 and absolutely nothing can be deduced for efficacy at this stage. It will go into phase 2 later this year and is certainly worth keeping an eye on.

“Why mention it then, Lee?”

Well, just a couple of weeks later, an Australian TV News Channel broke the story with the headline “Huge Break through”.

Following this article there was a bit of a flurry in the MND Community. This was nicely calmed by MND Associations around the globe to temper the excitement.

Being brutal, the claims of effectiveness made in the media story simply cannot be justified from the data published and the extent of the trial. The best thing about this media story is the awareness it creates. For those with MND there is nothing to see yet. Even in the 5 years since my diagnosis I have seen several drugs reach this stage claiming effectiveness only to not proceed, or fall apart later.

The second trial, that I thought I would mention, is a drug already in use in Japan for Asthma, Ibudilast. This drug is being tested as an additional add-on therapy with our one proven drug, Riluzole. It is an interesting approach, as it focuses on improving the effective aspects of Riluzole. As far as efficacy, the early Phase 2 trial data shows that this drug could have an effect. I mention this trial today as I wanted to describe one aspect of the reported data that niggles me and I suspect some scientists, but they are more coy than me!

This concerns the disease measure complexity

You might recall rom my post Exactly what state am I in?, how MND progression is measured. It is simply a questionnaire known as the ALSFRS-R rating scale, and you can actually read and complete one here. There is NO blood test etc.  This subjective measure is very problematic and is the main issue why trials are so long and complex. In the ibudilast study the researchers classified a positive “responder” in a novel composite endpoint. A responder was defined as any patient who showed less than a 12 points loss in a 12 month period. This is actually including people getting much worse!! A non-responder lost more than 12 points. To add to this, our natural disease progression can even include plateaus. So in my opinion, such a second degree measure is potentially problematic. I encourage readers to be careful in interpreting the data right now. Importantly, the trials on the drug continue, and to the pharmaceutical company’s absolute credit they are not pushing this drug faster than should be and moving towards a phase 3 where the effects can be verified. Let me be very precise here. I am not saying that the data interpretation is misguided, it is designed to try to potentially identify an early positive effect through quite novel methods. The phase 3 will be vital. Definitely worth watching this one!

If you have just read my Clubs post, there is, perhaps, a potential interesting aspect of this drug that I will write about in my next research post (see below).

As I have now been writing research updates for nearly 3 years, it is time for a level set. I have realised that many who read my blog are newcomers, but also sadly just in the UK over 2000 people join our community every year! So there needs to be a new summary post. That will be my next research post.