AMBRoSIA – our biggest ever research project

The AMBRoSIA (A Multicentre Biomarker Resource Strategy In ALS) project is our biggest, most ambitious research undertaking to date. The project funding began in August, closely followed by being the focus of this month’s ‘Make Your Mark’ fundraising appeal. Here we explain more about what this flagship project is all about.ambrosia-pic

This new five year research project, costing in excess of £2 million, will search for biomarkers of MND on larger scale than ever before. It will leave a legacy resource to improve diagnosis and our understanding of MND for the future.

AMBRoSIA will be nested in three world-class research centres in Oxford, London and Sheffield, and will be led by three of the UK’s top MND researchers – Prof Martin Turner (Oxford), Dr Andrea Malaspina (London) and Prof Dame Pamela Shaw (Sheffield).

Why do we need biomarkers?
A biomarker is a ‘fingerprint’ of MND – something that can be measured in the body that is unique to MND. Biomarker discovery would mean a faster diagnosis and a better understanding of the disease, which will lead to bespoke, effective treatments. You can read more about why biomarkers are so important in a previous blog.

The collection of good quality samples, from the same people over time, is at the heart of biomarker research – and that’s what AMBRoSIA is all about.

Who can take part?
AMBRoSIA will recruit 900 people with MND to take part. In addition, 450 people without the disease will also be recruited, for comparison (this is known as a control group). The control group will consist of 135 first-degree relatives of people with MND (a parent, sibling or child), and 315 people with no family link to the disease.

What samples will be collected?
Participants will donate blood, skin and urine samples on a regular basis. Where possible, cerebrospinal fluid will also be collected.

In total, it is expected that AMBRoSIA will collect over 250,000 samples across the five years of the project.

What will the samples be used for?
The samples collected will be stored across the three sites and will undergo a series of tests to search for biomarkers of MND. In addition, the skin cells will be used to create motor neurones using ground-breaking stem cell (iPSC) technology. You can find out more about iPSC technology on our website. Motor neurones created using iPSC technology will be used to screen potential new drugs.

Ultimately, the samples will form a new large-scale biomarker testing resource, which will be used to for future research.

How will the samples be analysed?
The lead researchers were all involved in the development of international consensus guidelines for the collection, processing and storage of samples of the highest possible quality. These guidelines will be used in the sample analysis for AMBRoSIA.

All the samples need to be processed using the same 'recipe'.

All the samples need to be processed using the same ‘recipe’.

The TV programme the Great British Bake Off illustrates the importance of developing guidelines for sample processing. Those of you familiar with the programme will know that even though the contestants may be given exactly the same recipe, their cake creations may turn out very differently! The researchers want the same results from using their ‘recipes’ in every centre!

What happens now?
The project is now in the crucial set-up phase. This includes setting up the structure of AMBRoSIA and its governing system, recruiting the scientists to work at each centre, and gaining the ethical approval needed to undertake the study. A Steering Committee is being formed, which will oversee the running of the project. This will comprise of research leaders, representatives from the MND Association and people living with MND.

How can I get involved?
As the study is still being set up, the researchers aren’t collecting samples yet. However, if you have MND you can let us know that you are interested in taking part by joining our research list.

When the researchers are ready to start collecting samples we will send out a letter to everyone on this list, explaining what to do next. There’s more information on the research list on our website. Please email us on our research@mndasociation.org email address if you would like to be added.

Could a Diabetes drug be useful in treating MND?

Today we announce a new collaboration for a preclinical research study on the diabetes drug liraglutide, in the hope that positive results will lead to a clinical trial in MND. Here’s a little more about the rationale behind the study.

The idea that drugs licensed for one disease may have some use in another completely different disease is not new, but it has gained much more attention in recent years. Researchers are developing a new understanding of disease processes, leading to new ‘drug repurposing’ opportunities, with the additional potential to reduce the time and cost of drug development.

Significant advances in genetics and molecular biology in recent years have greatly increased our understanding of the pivotal, carefully balanced cellular processes that usually keep motor neurons healthy but, when disrupted, can cause a cascade of degeneration leading ultimately to their death. Continue reading

ALS/MND Clinical Trial Guidelines: your opportunity to comment!

A few months ago we wrote an article about the ALS Clinical Trials Workshop which took place in Virginia, USA. Since then the Guidelines Working Groups have been busy turning the large number of issues debated into a first draft of a new set of guidelines. This is open for comment from 1- 31 August.

The guidelines will be posted on this website, and comments can be sent to guidelines.public.comments@gmail.com.

The guidelines are divided into sections:

  • Preclinical studies
  • Study design and biological and phenotypic heterogeneity
  • Outcome measures
  • Therapeutic / Symptomatic interventions in clinical trials
  • Patient recruitment and retention
  • Biomarkers
  • Different trial phases and beyond – (there are two sections on this)

Within each of these sections, there are many recommendations. The Clinical Trials Guidelines Investigators want to ensure that all interested people and stakeholders have an opportunity to provide input – whether you are a researcher, clinician or person with MND.

Thank you very much for your help.

For more information, please see a copy of their press release below: Continue reading

New genetic discoveries tell us more about what causes MND – Part 2

Two sets of MND genetic results were published yesterday. One of these results was about the importance of a new gene called NEK1. The second highlighted the role of gene C21orf2 in MND – we wrote an article about this yesterday. Both sets of results were published in the prestigious journal Nature Genetics.

What are the results and what do they tell us?

Researchers found that variations in the NEK1 gene contribute to why people develop the rare, inherited form of MND. Variations in the NEK1 gene were also found to be one of the many factors that tip the balance towards why people with no family history develop MND.

NEK1 has many jobs within motor neurones including helping keeping their shape and keeping the transport system open. Future research will tell us how we can use this new finding to target drugs to stop MND. Continue reading

New genetic discoveries tell us more about what causes MND – Part 1

Today some exciting news about the genetics of MND was published in the scientific journal Nature Genetics. The results come in two research papers published in the same issue of the journal.

This blog post discusses the results of the first of these papers for which King’s College London based Professor Ammar Al-Chalabi was one of the leading researchers. A post on the second paper will follow later.

Here we’ve given an overview of what the researchers have found, what it means for people with MND and how the analysis was conducted. You can read a more detailed explanation of the research results from the King’s press release. Continue reading

How faulty proteins disrupt waste recycling and disposal inside nerve cells

Researchers from the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield have uncovered a new function of the C9orf72 protein. A paper on their work has recently been published in the EMBO Journal.

A change or mutation to the C9orf72 gene is linked to about 40% of cases of inherited MND. We also know that changes to this gene also occur in a type of dementia called frontotemporal dementia (FTD). However, the reasons behind this link have so far been unclear.

One of the main research routes towards explaining the link between the C9orf72 gene and MND is to work out the normal function of this gene. By studying the protein the gene produces, researchers can see how alterations to this protein and the processes it is involved with result in nerve cell damage in MND. Continue reading

Motor neurone signalling and the effects of RNA in MND

Dr Pietro Fratta completed his first MRC-MND Association Clinical Research Training Fellowship in 2014. Last year he was awarded a new £1.16 million Clinician Scientist Fellowship to continue his research at University College London, studying the earliest physical changes that affect motor neurons in MND (our reference 946-795). Our contribution to this four year research fellowship is £280,000.

Pietro Fratta

Dr Pietro Fratta, University College London

As his first Fellowship progressed, Dr Fratta became more interested in the field of RNA biology, where he is rapidly establishing himself as an expert. His latest project aims to see whether RNA plays a pivotal role in the earliest signs of cellular damage that occur in MND.

RNA is the cell’s copy of our genetic material known as DNA; Dr Fratta is hoping to establish if the transport of RNA molecules along the nerve fibres is impaired and if so, whether there are particular versions of RNA that are particularly important for motor neurone health and survival.

Several lab studies have shown that the process of transporting things up and down the motor neurones is impaired long before the physical signs of damage are seen. His research will seek to find out what RNA molecules are present in both the cell body of the motor neuron and the nerve fibres. Continue reading

Identifying the genetic causes of MND in specific populations

Dr Russell McLaughlin from Trinity College Dublin is one of our Junior Non-Clinical Fellows.

Our Non-Clinical Fellowships were awarded for the first time last year. They aim to retain and develop early and mid-career MND researchers conducting biomedical research. These fellowships are funded for up to four years. We are currently funding two junior and two senior fellowships.

In this three-year research fellowship, which began in January, Dr McLaughlin is studying the more subtle genetic causes of MND (our reference: 957-799).

Why is genetic research important in MND?

We know that for approximately 5-10% of people living with MND, the cause of the disease is primarily due to a mistake within the genes. We also know that very subtle genetic factors, together with environmental and lifestyle factors contribute to why the majority of people develop the disease.

It is likely that these subtle genes are quite rare, and that is why we have not found them so far. As part of his research, Dr McLaughlin is hoping to identify the rarer gene variants that may be linked to MND. Continue reading

Using iPSCs to understand why motor neurones lose their normal function in MND

Researchers can create human motor neurones exhibiting signs of MND in the lab by taking skin cells from a person living with MND and reprogramming them into motor neurones. This is called induced pluripotent stem cell (iPSC) technology and gives an ‘in a dish’ human model of MND. iPSCs are being used by several of the researchers we fund.

GBMiles

Dr Gareth Miles

Dr Gareth Miles from the University of St Andrews, together with former PhD student Anna-Claire Devlin, has previously found that these ‘in a dish’ motor neurones lose their ability to produce an electrical nerve impulse. MND-affected motor neurones at first become overactive, and then subsequently lose their ability to produce the impulses needed to make muscles contract.

In his new project Dr Miles and PhD student Amit Chouhan, alongside Prof Siddharthan Chandran (University of Edinburgh), plans to use iPSCs to investigate why these electrical properties in nerve cells change in MND (our reference: 878-792).

The researchers will look at proteins called ‘ion channels’ that regulate the flow of electrical messages (called an action potential) which travel along the nerve cell towards the muscle. Continue reading

Transforming skin cells into nerve cells to understand MND gene mutations

In previous research Prof Kevin Talbot and colleagues at the University of Oxford began to understand more about how the C9orf72 gene defect causes human motor neurones to die. These studies were carried out using an impressive piece of lab technology, called induced pluripotent stem cell (iPSC) technology.

iPSC technology allows skin cells to be reprogrammed into stem cells, which are then directed to develop into motor neurones. Because they originated from people with MND, the newly created motor neurones will also be affected by the disease. Researchers can grow and study these cells in a dish in the laboratory. Continue reading