My view on the current road to a therapy – Jan 2017 Update

Here are my current observations on the move towards for what we all want, and that is an effective therapy for MND/ALS. This post is based on reading papers including symposium abstracts. No more, no less. I am a very optimistic person, but at the same time I temper my thoughts with realism and the rigours of scientific process. I might repeat some details from previous posts, but hey, that must mean they are important, yes!?

I would like to say the following right now and upfront.

All of the items mentioned in this post may fail. The full scientific trial processes need to run to completion.

And to date we only have one drug Riluzole. There is nothing new available.

Before I discuss the current drugs creating some interest in the MND community, a few words about potential drug effects and individuals.

Drug trials have historically focused on a statistically safe and significant effect across trial participants. It is becoming apparent, however, that although some trials can appear to fail, some trial members may have seen a beneficial effect. For example, in a couple of trials when participants are reclassified by “time since onset” or perhaps the “definiteness” of their diagnosis, new groupings have shown statistically significant effects with drugs which appeared at first to be useless. Interesting?

The simplest takeaway from this is that a combination of perhaps ‘small effect’ drugs may be the next key stage in treating MND/ALS. This may be just like HIV which hit the world in 1981. The first real effective treatment for AIDS was a cocktail of drugs throughout the early 1990s long before the game changing antiviral treatments that now make HIV survivable. Being realistic, I do believe this is also probably going to happen for MND/ALS before any major knockout therapy which is still probably some time into the future.

So where is research globally with, what I call, potentially ‘small effect’ drugs? There are currently several drugs that have reached various stages of human trials, and appear to be showing varying degrees of indicative mild effectiveness.

The drugs that I am currently going to keep an eye on with their progress over the next year or so are:

1) Masitinib

2) Edaravone

3) NP001

The first two drugs both appear to be moving forward, and are getting coverage within the community. Edaravone is actually already approved in Japan. For both of these drugs the precise effectiveness figures are not freely available. NP001 is a drug targeted at neuro inflammation, and is in very early trials. None of these drugs are available outside of the approved trials.

With MND there are several biological processes which lead to the disease. One of these is weaker and weaker nerve impulses from the brain. An interesting therapeutic approach that is being investigated is the ability to stimulate muscles to respond more strongly to weakening nerve impulses. Such a concept could be useful for many diseases, and not just ALS. For MND/ALS it might provide a way to increase the strength of certain muscles as they waste. It won’t be a cure, but again it is another drug that may appear in a potentially new shiny toolbox!

A drug being trialled for this approach is Tirasemtiv, and is actually the only drug in Phase 3 globally. Phase 3 is THE major trial stage where effectiveness on larger scale is proven or not. In fact, many drugs that appear to have some form of effectiveness in phases 1 and 2 fall dramatically by the wayside in phase 3. From earlier trials there was a significant tolerance problem with many patients having to leave the study because of side effects. But the study has continued, which is interesting. It is thought that the phase 3 results should be complete sometime in 2017.

The most exciting research areas, in my opinion, are the emerging gene therapy approaches. In 2016, the first apparently effective gene therapy for a Neurodegenerative disease has emerged. At the end of December a drug for SMA (Spinal Muscular Atropy) was approved by the FDA in the USA.  It is often known as a juvenile form of MND, as it typically affects children under one who rapidly deteriorate and die. Some quite dramatic results have been observed with children surviving and gaining motor function. The current cost of the treatment, Spinraza, is quoted at about $500,000 per child per year!! It does open a discussion on the complex subject of cost of new/emerging treatments. It is not as simple as “You can’t put a price on a life“, despite what we all might like to think. That’s a discussion for another day!

There are now two gene therapies being investigated, at very early stages for two genetic causes of MND, the SOD1 and C9ORF72 identified genes. Over the next 2 years we should start to see if one of these has potential. If these move forward, and I say if, we might just turn the corner in the approach to designing wider therapies for the 90% of cases that are not currently associated with specific identified genetic mutations,

My next research comment post, in a few weeks will focus on the word “environmental” as used in the following statement:

Researchers believe MND is caused by a mix of genetic, time (age) and environmental factors

Is it the best term to use? Intrigued?

I will leave you with this video courtesy of the ALSA from their YouTube channel and it is well worth a watch if you want to gain a deeper understanding of MND Research. Hear from the real experts.

It is a two hour “Ask the experts session” part of the annual ALS Symposium held last month in Dublin. It consists of 4 sessions

1) Current trials (30 minutes)

2) Stem Cell therapies – The Hope and the Hype (30 minutes)

3) Genetics and ProjectMinE (30 minutes)

4) Panel discussion (30 minutes)

If you are a keen reader of my blog you will know that I have commented on Stem Cell therapies specifically for MND. But don’t listen to me. Listen to Dr Jonathan Glass in both his 30 minute session on the hope and the hype of stem cell therapies, and then his answer to this question in the panel discussion in the video above. Dr Glass is one of the leading professors of neurology worldwide. An interesting answer!

Thank you for reading. Please remember that this is just my interpretation, as a patient with MND/ALS, of where research is going. For those of you also affected by the disease, please, please always listen to your neurologist. He/she will guide you. It is vital you discuss with them directly if you are considering any treatment options as yet unapproved.

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