Sheffield work towards a treatment for SOD1 form of MND

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.

Laboratory PhotoThe 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. Read the rest of this entry »

Project-MinE

Barbara Thuss is project co-ordinator for Project MinE, an international initiative with the aim of sequencing at least 15,000 MND genomes. We announced earlier today that the MND Association is funding the UK-arm of this initiative, known as the Whole Genome Sequencing project. Here Barbara explains more about Project-MinE.

Although the precise cause of MND is still unknown, in recent years it has become increasingly clear that this devastating and fatal disease of the motor neurons has a genetic basis. Project-MinE is an ambitious international research initiative aimed at detecting genetic causes and risk factors for MND. The project has been initiated by two people living with MND, along with the ALS research group in the Netherlands.

mine Read the rest of this entry »

The UK Whole Genome Sequencing project

Dr Samantha Price is the Research Information Co-ordinator at the MND Association. As well as organising the ‘blog a day’ during MND Awareness Month she also communicates the latest news about MND research. Here she blogs about the MND Association’s announcement of the UK Whole Genome Sequencing project.

It’s been a brilliant Awareness Month with blogs about zebrafish research and streaking meerkats. To end on a positive research note, we’re delighted to announce that we are funding a UK Whole Genome Sequencing project to help us understand more about the causes of MND. Utilising samples from our own UK MND DNA bank; researchers in the UK will aim to sequence 1,500 genomes to help identify more of the genetic factors involved in the disease.  Read the rest of this entry »

Another piece in the MND Jigsaw..

TDP-43Research published yesterday on 3 June 2014 in the prestigious journal Nature Communications, highlights key insights into how the protein TDP-43 may cause motor neurones to die in MND. Association-funded researcher Prof Chris Miller based at the Institute of Psychiatry at King’s College London, was involved in the research.

In the majority of cases of MND the protein TDP-43 is found to form pathological clumps within the motor neurones. The build up of this protein is thought to cause the motor neurones to die in MND, however researchers are yet to identify how this happens.

Association-funded researcher Prof Chris Miller has identified that the protein TDP-43 causes the connection between two cellular compartments within the cell to loosen. The breakdown of this connection means that the mitochondria (the cell’s battery) and the endoplasmic reticulum (where proteins are made and recycled) can no longer communicate and work together.

By identifying this target within the cell, the search is now on to find drugs to restore the strength of this link. Read more about this news story on our website.

Only four days in and it seems that MND Awareness month is going to be anything but quiet.

Tirasemtiv Phase II clinical trial – results

The top-line results from the Cytokinetics Inc Phase IIb clinical trial of Tirasemtiv were announced last week. Following this announcement, detailed results were then presented on 29 April 2014 at the Annual Academy of Neurology (AAN) meeting.

Unfortunately, although the drug was found to be safe, the results concluded that Tirasemtiv did not meet its primary objective, showing no difference in disease progression, as measured by the ALS Functional Rating Scale (ALSFRS) compared to placebo matched controls. Cytokinetics Inc have stated that further study of Tirasemtiv is needed.

Read the rest of this entry »

The Medical Innovation Bill

A lot has been happening in terms of research policy at the moment, from the announcement of the European adaptive licensing pilot to the Government’s Early Access to Medicines scheme. The newest addition is the Medical Innovation Bill. But, what does this Bill mean? How is it different to the other initiatives and why are we not supporting it?

What’s the difference?

The idea of adaptive licensing is that medicines should be licensed for use in patients more quickly. The Early Access to Medicines scheme announced earlier this month is run by the Government and, in principle, hopes to speed up the process by making drugs available several years before they are licensed. The net result should be much the same – earlier access to promising new drugs – but the UK scheme is already operational and should start having an effect more quickly. Read the rest of this entry »

Tirasemtiv – detailed trial results to be announced next week

Cytokinetics have published a press release of their ‘top line’ results for their drug Tirasemtiv. Unfortunately, the results are disappointing.

The main aim of their most recent clinical trials was to see if there was a slower rate of progression (measured by a widely used MND clinical scale called the ALSFRS) in people with MND taking tirasemtiv compared to those taking the dummy drug. The researchers didn’t find any difference in ALSFRS scores. They’re currently analysing the results for beneficial effects on other symptoms of MND.

The full results will be presented at the American Academy of Neurology conference next week. Sam is working on a more detailed article after these have been presented.   More information about tirasemtiv can be found on our website. The press release announcing these ‘top line’ results can be found here.

Dr Belinda Cupid, Head of Research at the MND Association said: “MND clinical trials give us all new hope that something can be done to slow the progression of the disease, and it’s devastating when those trials don’t show any benefit. It emphasizes why we have to continue to fund research – finding the cause and source of the disease and then working out how to stop it.”

Early Access to Medicines scheme

Last month the UK Government’s Department of Health announced an Early Access to Medicines Scheme. But, what is this new scheme? and what does it mean for people living with MND?

The drug trial processpipette

The only proven drug to slow progression in MND is riluzole. This is the only drug that has passed all the stages of drug testing – known as clinical trials – and has been shown to be beneficial for people living with MND. Clinical trials are the ‘gold standard’ and are put in place to ensure that a drug is safe and beneficial before it is given to patients.

Read the rest of this entry »

What’s all the ‘FUS’ about?

Prof Vladimir Buchman (Cardiff University)’s research was selected as one of the best research studies, as decided by the journal editors, published in the Journal of Biological Chemistry in 2013. He is building on this research in his Association-funded project, which began on 1 April 2014.

The background to FUS:

In 2009 an international team of scientists, including researchers funded by the Association, identified the FUS gene as a cause of approximately 4% of inherited MND cases (5-10% of total MND cases).

The FUS protein formed by this gene is usually found in the nucleus or ‘control centre of the cell’. A change in the structure and/ or function of the FUS protein leads to motor neurone damage and the development of MND. This change causes the FUS protein to ‘wander’ outside of the cell nucleus and form protein ‘clumps’ within the cell.

These protein clumps, as well as being found in 4% of inherited MND cases, are found in many cases of MND and the related disease, frontotemporal dementia. At present it is still not clear how this happens and how these clumps of FUS protein cause MND.

Read the rest of this entry »

Switching the light on for MND

MND Association-funded researcher, Prof Linda Greensmith, based at University College London, together with her collaborator Dr Ivo Lieberam from Kings College London, have introduced stem cell-derived motor neurones into mice. Published in the prestigious journal Science on 4 April 2014, her research has also demonstrated that muscle function can be controlled by light.

Modelling MND

MND Researchers use a range of models to further our understanding of MND. These can be animal models, such as mice and zebrafish, or cellular models, such as induced pluripotent stem (iPS) cell-derived motor neurones (as described by Association-funded researcher, Dr Ruxandra Muthiac, during the Spring Conference in Newport on Sunday 6 April).

These models enable us to find out more about the causes of MND by studying how changes in the genes (our genetic makeup) give rise to MND. Not only this, models of MND are the essential ‘first step’ in screening potential new MND drugs before they go on to human trials.

Prof Greensmith and her team of researchers used an early stage mouse model of MND. By using this model she was able to investigate if embryonic stem cell-derived motor neurones could be successfully transplanted into mice and whether muscle function could be controlled by light.

Read the rest of this entry »

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