A number of articles were published in various news sources on 11 July 2014, highlighting how scientists in Sheffield are working towards testing a promising treatment for a rare inherited form of MND caused by the SOD1 gene. Here we write about the research and what it means for people living with MND.
The Sheffield Institute for Translational Neuroscience (SITraN) specialises in research into MND and other neurodegenerative diseases. Recently the institute received an anonymous donation of £2.2 million to help translate their research from the lab to the clinic. This is a huge amount of money into MND research and this donation will enable the researchers to further our understanding of the disease.
The research
We know that approximately 10% of cases of MND are inherited. This means that they are characterised by a strong family history and the disease is caused directly by a mistake in a specific gene. Of these 10% of cases, 2% are caused by the SOD1 gene (meaning that for every 100 cases of MND, 10 cases are inherited and of these, only 2 are directly caused by the faulty SOD1 gene).
Prof Mimoun Azzouz’s research at SITraN was reported in a number of news outlets, highlighting how his research is paving the way to a treatment for a rare form of MND. His research is at a relatively early stage, where he has only just begun investigating the use of a technique known as ‘gene therapy’ in mice affected by the SOD1 inherited form of MND. If the research goes to plan, he will be able to submit a proposal for regulatory approval by August 2015.
Regulatory approval is the process where a researcher submits an application for a clinical trial to the Medicines and Healthcare products Regulatory Agency (MHRA), who then review the application. It is only after approval has been granted, clinical trials will then start.
What is gene therapy?
Gene therapy is a technique where researchers treat a disease by preventing, and blocking, the faulty gene. In this case, Prof Azzouz is aiming to block the SOD1 gene.
The SOD1 gene corresponds to the SOD1 protein (see baking with genes and proteins as to how this occurs). When this gene is faulty in some inherited forms of MND, this means the resulting protein is not formed correctly and unable to do its job. The idea behind Prof Azzouz’s gene therapy research is to inhibit this gene, and stop production of the resulting protein, reducing the amount of SOD1 within the motor neurones.
The way in which gene therapy works, is a bit like a car company that produces a number of different cars. If the car company identifies that one of the car models is faulty (eg a white Ford Fiesta), then someone would go into the factory and stop that specific technician making that specific car. This would mean there would be less faulty white Ford Fiestas on the road, resulting in fewer accidents.
In this analogy, the person stopping the technician in the factory from making the white faulty cars is the gene therapy treatment, with the faulty SOD1 protein being the faulty white Ford Fiesta. As we inherit two copies of each gene, the healthy SOD1 (eg a blue Ford Fiesta) is still produced by another technician but the faulty SOD1 is not.
Therefore, the aim of the gene therapy treatment would be to stop the faulty SOD1 gene from making the SOD1 protein (the white Ford Fiesta), without affecting the healthy SOD1 (the blue Ford fiesta). This would result in less faulty SOD1 protein within the motor neurones, ultimately delaying the progression of MND.
Treatments for SOD1-MND
SOD1 was the first MND-causing gene to be discovered back in 1993, and as such we are beginning to see research into SOD1-specific therapies. Prof Azzouz’s research complements other SOD1-specific therapies, such as the ‘antisense therapy’ ISIS 333611.
In April 2013 we announced the results from the phase I clinical trial of ISIS 333611. Working in a similar way to Prof Azzouz’s research, this therapy interferes with the SOD1 genetic material by ‘hiding’ part of the gene, meaning that they are silenced when the final protein is made.
SOD1-targeted therapy is becoming a ‘hot topic’ in the MND research field and as a result research into this area will be discussed in a dedicated session at the forthcoming 25th International Symposium on ALS/MND in December 2015.
In summary
The announcement of Prof Azzouz’s research highlights a huge investment of £2.2million into MND research at SITraN.
Director of Research Development, Dr Brian Dickie, said: ““SOD1-specific therapies are leading the way in approaches to develop more personalised treatments for specific subtypes of MND. Inherited MND caused by the faulty SOD1 gene accounts for a small proportion of MND cases, however gene-therapy approaches may open up ways of treating other forms of inherited MND in the future.
Although Prof Azzouz’s research is encouraging, it must be stressed that this research is still in its infancy, with the results in mice still to be analysed. However, if results are positive (as they have been in previous mouse studies where the SOD1 gene has been inactivated) then SITraN is perfectly placed to transfer this knowledge from the lab to the clinic.”
It is also important to note that if a clinical trial of this treatment is approved, it would only be a safety trial at first (known as a phase I clinical trial), as this treatment has never been tested in humans before.”
Dear sirs I have been looking at a website where they say in Japan they could help me with treatment with muscle tension and variable treatment with my MND i am very tempted as I would do anything if it would help my illness . Would you recommend it I wondered and is there any truth in it . Best Regards Mrs P Collins
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I also know someone is going to Germany who I write to on MND awareness group
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Dear Mrs Collins,
The only proven treatment for MND is Riluzole, which has been shown to delay the progression of the disease. Non-invasive ventilation has been proven to increase quality of life in people living with MND who have breathing difficulties and a drug called ‘NUEDEXTA’ for some people with MND who experience psuedobulbar affect is currently undergoing the process of applying for a UK license.
There are a number of clinical trials underway for MND, however at present no treatment other than Riluzole has passed these trials showing a beneficial effect in MND. Therefore it is likely that the treatment you are referring to is unproven, however if you email research@mndassociation.org with details about the treatment I can then look into it further to establish whether or not there is any science behind the claims?
Kind regards,
Samantha Price, PhD
Research Information Co-ordinator, MND Association UK
In mid august 2014 i did at sheffield hallamshire hospital give spinal fluid and tissue sample in the research into s o d 1 as i have that form of m n d which was diagnosed aug 2012 if the trials are succesful do you think it would be of any help to me or would it only benefit sod 1 carriers who have not yet developed the disease
Dear John,
Thank you for your email. In terms of this research at Sheffield, we’re unsure as to what the criteria will be if this treatment makes it to the clinical trial stage for MND. It is possible that it will be offered to people with the SOD1 inherited form of MND, as this is what the treatment is aimed at, but we will not know until this treatment gets to this stage of testing (the researchers are still testing in mouse models of MND).
If you have any further questions about MND research please do not hesitate to contact me on 01604 611 880 or via research@mndassociation.org.
Kind regards,
Samantha Price, PhD
Research Information Co-ordinator
MND Association, UK
Pleased to report that I have now had five full trial doses and have not shown any side effects soon there will be a short film on you tube showing the treatment at the hospital and a little about my home life,Many thanks to Professor McDermott ,Doctor Jonathan ,Senior nurses Helen and Theresa for all their dedicated care,not forgetting the people who help that we don’t see
Mr.Shantanu Chadokar
Sir i am male 25 years old i am suffering from monomelic amyotrophy since 5 years i was diagnosed in 2009 can gene therapy be beneficial for me.Can this therapy improve the symptoms of such non progressive mnd diseases waiting for your reply.
Thank you
Dear Shantanu,
Thank you for your comment – this research is still in the relatively early stages and further research is needed to confirm whether this treatment may or may not be beneficial in MND. The therapy is targeted at the SOD1 gene associated with causing a small number of cases of MND, however it is not known yet whether or not it will be beneficial in this form of MND.
Kind regards,
Samantha Price, PhD
on behalf of the Research Development team
research@mndassociation.org
Thank you so much madam for your reply.But with so much research and trials are going on is there a possibility that in near future probably 3 to 5 years there could be a cure for such disease or even improving half symptoms because that is all i need as only a small portion of my opposite is affected so even if they find a way to reverse a bit of symptoms it would be like normal.
Dear Shantanu,
There is more MND research underway today than there has been at any other time. In terms of research, this year two new inherited MND-causing genes have been identified and a number of other significant discoveries have been made.
Timeline for developing treatments are difficult to state but if you email research@mndassociation.org we can send you further information about current research in this area?
Kind regards,
Samantha Price, PhD
on behalf of the Research Development team
MND Association, UK
Hello ,
I am suffering with mnd and I am feeling very nice to know that there is some research going on to help people like me but my family wants to know when gene therapy would be available in clinics .right now I am taking riluzole.Thank you.
Hello,
Thank you for getting in touch.
Gene therapy as a treatment for MND is still in the early stages of development and research. The treatment mentioned in this blog is looking at the types of inherited MND, which have a strong genetic cause.
In the UK it has not yet entered the clinical trials stage, where they test a treatment to see if it is safe and if it works at helping to slow MND progression. Therefore gene therapy is not available in clinics at the moment.
If you have any more questions please email them to research@mndassociation.org.
Warm regards,
Sara Bolton, MND Association UK
Hello,What type of a diet could i opt when i am suffering with mnd ?thank you.
Hello,
There is no special diet available for people with MND to follow, but the best advice is to eat a varied and balanced diet. Staying well nourished is one of the most important ways to counter the effects of MND. A dietitian may be able to advise you if you need supplements or fortified foods, depending on your current diet.
Warm regards,
Sara Bolton, MND Association UK
Hi there,
Do you have any update on the SOD1 trial, can we expect it soon? My family need it sooner rather than later 🙁
Regards,
Mary
Dear Mary,
Thank you for your comment. We have no heard anything further from the team conducting this research in Sheffield. Their research is still in its early stages.
There is similar work being carried out elsewhere into gene therapy, and more information on this was presented at the International Symposium on ALS/MND last year. My colleague wrote a blog post on it, which can be read here
Kind regards,
Sara Bolton
MND Association, UK
I live in New Zealand and have MND since my final diagnosis in late 2014 I have not seen a Neurologist and have not been given another appointment by the Neurologist who made the diagnosis which I find rather disappointing as I have no way of knowing how well or not I am doing and at what stage I am at only by what I have researched myself. I have the Bulbar MND it started with speech and has progressed to swallowing and I now have a peg for feeding. I do find eating now a struggle so most of my nourishment is via the peg. I read with interest the developments of research into what causes MND which is a minefield in itself let alone a cure being found. I just hope that one day a cure or control for this terrible hideous disease will be found.
It is encouraging to follow this research and I do so with great interest. Thank you for allowing us to share this progress.
I am the Carer to John Wood who is under going the SOD1 trial st Sheffield institute in the of Research Neuroscience and has recently reply to your blog. John has been amazing as he’s was the first participant to start the trai which has been a challenge to him and myself. The multiple doses have finished but he stil has 7 months of test for monitoring which include a further 2 lumbar punctures.
The team have been fantastic and extremely supportive and we would like to say thank you to everyone involved
Valerie & John Wood
My name is John Wood also known as Les wood as can be seen from previous posts I am the first person in the u k to have a new treatment for S O D 1 type M N D I completed the trial stage around March 2017 . Every thing went well and the trial took about 6 months ,around 7 others took part in the trial.The treatment was given the go ahead to start in December 2017 its starts with 3 treatments inside 4 weeks this each time involves a Lumber Puncture whereby they remove a quantity of spinal fluid they then inject into the same point a quantity of the experimental drug .the 3 doses kick starts the treatment process it then goes 1 treatment every 28 days for 9 treatments after that well I don’t know what happens,I suppose it depends on the final results.However I am pleased to announce that just after my 3rd booster in jection mid December I managed to do some short walks around my bungalow without my 2 walking sticks this the first time in over 2 years.Now I do not want to give false hope to any one but I can of course only report on facts ,if I continue to improve is of course unknown but I have to say I am very hopeful of a little ( at least )improvement in my quality of life.A film of my walking was submitted by my wife to the Sheffield research team who are looking after me
Hi John Wood here( Les ) it’s now NOVEMBER 2019 and I’m extremely happy to report that my SOD1 treatment is still ongoing at Sheffield Hallamshire Hospital it’s every 28 days which though has been involving long days as much as 11 hours on occasions which I have always been happy to do.However the treatment has altered now and I now receive 100 mils of the drug still every 28 days but now I only have to lie down for 1 hour after the lumber puncture instead of the previous 6 hours this make life so much easier.Everything is still going well and I’m still enjoying life and I am pleased to say still enjoying 3 to four holidays a year thanks to my wife and carer Valerie who as a retired trained nurse makes for the perfect carer.I am now after 4 years on first name terms with all the doctors and nurses and always enjoy meeting them each month,I will try and update my news every 6 months or so ,thank you for reading my short accounts of my journey
Hi I am Les Wood this is a update on October 3rd 2018.well is six years now since my diagnosis in August 2012 I am pleased to report that I am alive and kicking ( still ) the SOD1 Treatment is still on going the drug has recently been in creased from 29 to 60 mgs and all is good although I use a wheelchair most of the time I am also able to get about with my two sticks,recently I had a blood clot on my lungs this was not caused by the treatment but most likely caused by my lack of mobility due to a chest infection and being in bed for four days moral is try and keep moving as much as you are able and keep your airways clear,not easy for every one of course.So to say I am pleased with the new treatment is an understatement,the Neuro Team at Sheffield Hallamshire Hospital are fantastic and a real credit to the N H S I cannot praise them highly enough