Please note this post was written over 4 years ago in 2016. However, I thought I should republish it as it is still very relevant today. In addition I am writing a new, more in depth Strategies with MND research approach post in my devil is in the detail series. But for now, please enjoy this now rather aged post………

Oooh Lee, what a posh title! Are you going all Melvyn Bragg on us? For my American readers, no sorry my international readers, Melvyn is a very intellectual, smart, and charming Television/Radio broadcaster who used to host amazing and thought-provoking discussions in the UK. However, Lord Lee Bragg, no relation, has kindly helped with this week’s post.


Lord Lee Bragg pontificating on the deteriorating moral fabric of British society in 1985 just before his mysterious 2 week absence following a bus trip to Brighton.

I promised you a serious blog this week, and here it is.

My post is about – “How do we find a solution to MND/ALS as quickly as possible?” I use the word solution, as opposed to cure, as it may not be entirely clear as to what the best way forward is. This will be one of several posts giving you a bit of knowledge of the disease and also a bit of onein300 wisdom!

I want to use this first post to give you the clear message that we will find an effective therapy for MND with the right research but also

1) Provide an insight as to why it is taking so long

2) and what can we all do to make this as efficient as possible

There is absolutely no doubt we are moving at a pace now with regards to the disease understanding. To give you a feel for how fast we are moving – twenty years ago we knew of 1 just genetic marker associated with the disease. Now we know of about 100 and the discovery rate is escalating dramatically. But we still have no effective therapy as yet. Just why is this?

I introduced some of the ideas in this post on my Research page, but I just want to place some thoughts in your mind that you could use at a dinner party. You know the sort of party. Conversation is going at a pace, and you are sat next to the party bore or “know it all”, and you desperately need to say something deep and thoughtful.

Firstly, what do we really know about MND disease causation?

Well we know a lot about what visibly happens to the body. However, most of what we know about the inner workings we have learnt from autopsies and animal models. Crucially, there is actually no diagnostic test for MND. This has two implications; firstly diagnosis can take a long time and along with it the uncertainty and stress of the sufferer and family. However, there is a not so obvious, but incredibly damaging, second implication of this lack of a test. It will become apparent as you read on, my refined readers……

Also, what do we mean by causation, and is a search for a cause the right way ahead?

“Lee, you imbecile, of course it is!!!!”

Ok, I need to be more precise in my terrible use of the English language and what I mean in this post by the word “cause”.

Many people, often when discussing the disease, say

“Is it some illness, or factor in the environment?”

“Hey Lee you exercised a lot, perhaps that has something to do with it?”

“Hey Lee, is it something in our diet?”

“They should look pesticides, diesel, etc”

The list is endless.

To me this is an absolutely critical point. Is it worth searching and analysing the whole environment? To a lot of people, finding a cause is just this, ie analysing factors with disease subjects. I won’t go into the detail as to why, but such research is incredibly difficult, hugely expensive, is nearly always biased and often extremely subjective. And of course, infinite!

My opinion is NO, it is not worth proceeding this way.

It goes to the root of a little bugbear of mine, and that is inappropriate and poor research. This is not restricted to MND research but to many scientific endeavours.

Research is very expensive, and it must be targeted and strategic.

I read a lot of research that at first glance is interesting, but on second read doesn’t seem to help, and on further analysis is next to useless!  The worst research, in my view, often is that which has this most annoying phrase written at the end:

“It is not known how the complex interplay of factors may affect x. More research is needed.”

Apologies to any perfect research that has this statement. I just find it an annoying phrase!

It is no surprise that the public can get frustrated with slow research. Readers, please be aware, before you get concerned, I am a massive science supporter!

I have read research on things such as exercise and MND, diet and MND, specific occupations and MND etc. In my opinion they are of very little use. For example, there is some evidence from a study of overall nutrition that more calories may help quality of life. However, this is pretty darn obvious and does not really warrant any further direct research.

“Hey Lee, but you say research is the only way forward”

Yes it is, and we must make sure it is carefully considered. I want every penny/cent donated to be used most wisely. I’ll tell you how later.

So what are the targets?

Absolutely the most efficient way to approach complex disease research is to understand at a cellular and biochemical level what is happening. It may then be possible to change that process. A potential therapy may then be either a new drug, existing drug, lifestyle change, physical intervention or even an external factor alteration for some identified individuals.

Any research that just keeps trying to analyse environmental factor after environmental factor along with MND/ALS patients is simply so unlikely to find the key. Yes you might stumble across it, Serendipity, but I wouldn’t rely on that. The fact that eating custard creams on a Sunday, whilst drinking red wine and sun bathing actually triggered this chemical change is irrelevant. The disease process is the key.

It’s a very interesting disease as we are all generally exposed to the same chemicals and environmental factors. For example, diesel fumes, pesticides etc, but not all of us develop the disease. Pure logic points us at “something special” about those who develop it.

This is why I support the ongoing ProjectMinE to understand absolutely the genetic and epi-genetic differences between those who develop MND and those who don’t.

Now back to the lack of a diagnostic test for MND.

The enormous issue this creates is that it makes the search for a treatment for MND vastly laborious. There is often a lot of criticism of scientists regarding medical trials and how long they take. Unfortunately, our most eminent scientists are not slow, it is this lack of a test that truly holds them back.

Unlike most diseases, when a drug is tested, we don’t actually yet have a biochemical measure of the effect! Compared to say HIV, where we can measure the amount of virus in the blood following application of drug x, we have no such luxury! For HIV we were able to screen compounds quickly. Have a guess how it is evaluated for MND?

We utilise a questionnaire, known as the ALSFRS-R score! I will talk about this in a future post. But simply put, it is no more than an assessment by talking to, examining and observing the patient!

“Ok Lee, so why does this explain why it’s taking so long?”

Well the key issue with this is that it dramatically (I mean enormously) increases the time for trials. You cannot simply measure the effect after 1 week. The effects take over a year to see any even small potential statistical changes! And of course, this questionnaire is only for people who show symptoms! The disease has almost certainly started a long time before any physical signs appear.

So in tandem with understanding the disease process, we have this serious measurement issue.

The second key area of research, in my opinion, is searching for these Bio Markers. This is the method of accurately and rapidly detecting the progress of the disease. I certainly believe that once we find markers, we are going to be able to perhaps detect the disease potentially decades before it shows itself! Critically once we have the markers, we will be able to test compounds rapidly (very rapidly).

There are 3 or 4 Bio Markers currently in late research which are close to being useful. This is exciting stuff!

So what have you learned from this post?

1) If you are going to donate some of your hard-earned money to research, please do it via your local Motor Neurone Disease Association who have excellent research teams who sift research proposals and allocate donations Strategically and wisely. Please don’t donate to ad hoc research, or also be swayed by some media. But please do donate, we need the money!

2) Two of the key areas are Bio Markers and full genome analysis.

3) Fruitlessly examining the environment is a waste of time. Without a decent measure of disease, I see it as a poor use of research funds.

So if Christmas and New year left you with a few pounds or dollars spare, please donate directly to the MNDA, ALSA in the USA or ProjectMinE.

My very last point in this post is actually very difficult for me to put on paper, but I will. As a person with MND, I feel I probably have more right to say it than other people. Over the last few years there have been 2 or 3 claims of a “wonder drug”. From a totally analytical and scientific view, they have been so far, lacking in substance. And yet, media, and now with social media, campaigns can begin, totally well-intentioned, trying to bypass crucial scientific processes. I won’t name any such drugs, but those of you with MND will know the drugs. I live an evidenced based life, and I just cannot support something which is based on limited evidence.

Well yes that was a serious post! It will have to be a silly one next week. I can’t expect you, my loyal subjects, to put up with this for two weeks in a row!

To finish up here is an example of my bugbear. What do you think my view of this research and report is? Have a read of the BBC report, and then click on the second link to see the actual “scientific paper” in the Lancet. This was serious funded research in 2015.

Lancet paper

A good use of research money?

Onein300 signing off for the week!


5 thoughts

  1. Great post. I am a researcher myself, studying and tries to find new and better diagnostic tools for a nother group of “rare” disorders. These disorders were also considered rare until exom sequnecing technology were avalible. Now these disorders has increased from 7 know in the begining of the 90 to over houndred today. So yes, genomics is a powerful tool. But it is crusial to understand that genes are just information, and you get a lot of information from the technique. The challange is to find the right one. Thus, genomics must, in my opinion, be combined with proteomics.
    Although there is no MND biomarker, there are biomarkers for neuron degeneration to be used to monitor potential drugs or co-variation with potential specific MND biomarker. Neurofilament in cerebro spinal fluid is one.
    I hope there is some seroius reseach conducted, because this disease is not really more diffiicult than Parlinson, alzheimers etc. It is just not yet investigated as much. Sorry for my long and maybe to technical comment.


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