11th Lady Edith Wolfson Clinical Fellowship awarded

We are delighted to announce that Dr Arpan Mehta has been appointed as our latest Lady Edith Wolfson Fellow, jointly funded by the MND Association and Medical Research Council.  This clinical research training fellowship will help to launch his career as an aspiring academic neurologist, providing comprehensive training in cellular, molecular and bioinformatics technologies in a world-class environment. 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

Using DNA Bank samples to create iPSC models of MND

Induced pluripotent stem cell (iPSC) technology has enabled researchers to create and study living human motor neurones in the lab, derived originally from patient skin cells.

DNABankLogoThis project (our reference 80-970-797) is a collaboration between the labs of Professors Chris Shaw and Jack Price at King’s College in London and Siddharthan Chandran in Edinburgh. It aims to use the already collected white blood cell samples within the UK MND DNA Bank to create a larger number of new iPSC models of MND. Ultimately creating an MND iPSC cell bank, these models will enable researchers to better understand the disease and screen potential new drugs. Continue reading

Season of mists and mellow fruitfulness…..and prizes….

The fantastic news that Patrick Joyce and his co-inventors have won the 2015 Hackaday Prize for their ‘Eyedrivomatic’ invention is one of a number of research prizes announced this autumn.

Martin Turner award

Prof Martin Turner receiving his award from Prof Jane Dacre, RCP President

At the beginning of November Prof Martin Turner was presented with the Graham Bull Prize for Clinical Science by the Royal College of Physicians (RCP). The Prize is awarded to a member of the RCP under the age of 45 who has made a major contribution to clinical science.

The winner of the Graham Bull Prize is also invited to deliver the prestigious Goulstonian Lecture, an annual lecture given by a young RCP member that dates back to 1635 and the list of previous speakers reads as a ‘Who’s Who’ of the history of British Medicine!

Those of you who know Martin, in particular the many participants who volunteer for his BioMOx research programme will be pleased to see his new title: he was awarded the title of Professor by the University of Oxford in July this year. Aren’t Professors getting younger looking these days…! Continue reading

Endomicroscopy – lighting the way for a diagnosis

Richard Ribchester 2015At present there is no diagnostic test for MND, and diagnosis is usually determined through clinical observations and by excluding other diseases. Because of this, a definitive diagnosis of MND can take up to several months.

By developing an effective diagnostic test for MND, we will be able to diagnose MND earlier and put in place effective care and support needs sooner. Another benefit to earlier diagnosis would mean that people living with MND can be started on riluzole much earlier. Continue reading

Giving voice to people living with MND: Voice Banking

Phillipa Rewaj, Rebecca Devon and Shuna Colville from the Euan MacDonald Centre for MND Research, University of Edinburgh, help us celebrate Global MND Awareness day. This year’s theme is ‘voice’ and here the researchers provide us with an update on their pioneering ‘voicebanking project’, which is part-funded by the MND Association.

 

Ring ring….ring ring….

“Hello?”

“Hi there, it’s me.”

“Oh hello dear, how nice to hear from you!”

 

Sound familiar? How many of your friends or family could you recognise from a few words of their voice? Two, five, ten or more?

It may have never previously occurred to you, but our voices are as unique as our face shape, our walk and even our eyes. A person’s voice is an essential component of his or her identity.

Continue reading

A stem cell route to the roots of MND

Nina Rzechorzek's article 'A window into brain disease is only skin deep" was shortlistedNina Rzechorzek is based at the University of Edinburgh. In 2012 Nina’s article on Prof Siddharthan Chandran’s research was shortlisted for the Access to Understanding Competition. Here she gives an update on his stem cell research.

It was a typical morning – trying to juggle experiments, trying not to make mistakes, trying hard to get results….sometimes life can be very ‘trying’ indeed… but then I’m not affected by motor neurone disease (MND) – and what a privilege it is for me to be able to rush around, to go to work and, hopefully one day, discover something that can make a difference.  I am reminded of this as I stumble out of the morning into a less ordinary afternoon – stepping away from the bench and into the world of my boss, Prof Siddharthan Chandran. Continue reading

Understanding Spinal Muscular Atrophy: could plant derived compounds hold the key?

On 3 March 2014, researchers based at the University of Edinburgh published a research paper that extends our understanding of the childhood disease – Spinal Muscular Atrophy (SMA).

Although this is not MND so-to-speak, the disease does affect the motor neurones. Plus, the results were so interesting; I couldn’t resist writing a blog post about them.

Floppy baby syndrome

SMA is a childhood disease of the motor neurones and is sometimes known as ‘floppy baby syndrome’. It affects 1 in 6,000 births making it more common than MND, which affects approximately 1 in 100,000 people.

Continue reading

Screening for Cognitive and Behavioural Change in MND

sharon abrahams and princess royalMND Association-funded researcher Dr Sharon Abrahams (University of Edinburgh) has recently published an article on the Edinburgh Cognitive ALS Screen (ECAS) in the prestigious journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.

It is now recognised that, in up to 50% of people living with MND not only the motor system (walking, talking breathing etc) but also other areas of the brain, particularly those involved in thinking, language and behaviour are affected.

Frontotemporal Dementia

Cognitive and behavioural changes are increasingly common in MND. It is also well known that a small proportion of people living with MND display features of frontotemporal dementia.

Continue reading

MND stem cell study identifies TDP-43 astrocytes as not toxic to motor neurones

Funded by the MND Association, international researchers have used stem cell technology to learn more about the relationship between motor neurones and their support cells.

These findings highlight the potential of stem cell technology as a tool to create new human ‘in a dish’ cellular models of disease to learn more about the causes of MND.

Prof Siddharthan Chandran and Sir Prof Ian Wilmut at University of Edinburgh looking at a stem cell image

The research group included MND Association funded researchers Prof Siddharthan Chandran and Sir Prof Ian Wilmut from University of Edinburgh, Prof Chris Shaw from King’s College London and Prof Tom Maniatis from Columbia University in America.

This important finding was published in the scientific journal PNAS on 11 February 2013. This new finding follows on from previous work published by this research group in 2012 where they demonstrated the proof of principle of creating human motor neurones with MND in a dish.

Why we need an astrocyte model of MND

Astrocytes, so called because of their star-like appearance, normally act as neurone support cells to nourish and protect motor neurones. They act with motor neurones to ensure that they can continue to function.

From previous studies, we know that when these cells begin to dysfunction, they can become toxic to motor neurones to contribute to MND. Finding out why astrocytes can cause motor neurones to degenerate is an issue of ongoing debate – we recently gave an update on this from the International Symposium.

Being able to grow human astrocytes in a laboratory dish is of importance to be able to learn more about the relationship between astrocytes and motor neurones in MND.

Creating human astrocytes in a dish

Using cutting-edge stem cell technology, the research group reprogrammed skin cells into astrocytes in a laboratory dish. The skin cells were donated by people with MND who have a family history of the disease caused by known mistakes in a gene called TDP-43.

Led by Prof Chandran and colleagues, the research group aimed to identify whether these cells would develop the ‘hallmarks’ of MND in a laboratory dish.

By studying the characteristics of these human astrocytes with faults in the TDP-43 gene, the research group identified that they shared the same qualities as cells affected by MND. The astrocytes had increased levels of TDP-43 found in areas where it isn’t usually found – outside of the control centre of the cell. They also found that the astrocytes didn’t survive as long as astrocytes created from skin cells of people that didn’t have MND.

This means that the human astrocytes created by Prof Chandran and colleagues using stem cell technology develop MND-like characteristics. This new model can be used to study how motor neurones develop the disease in a system that is directly relevant to people living with MND.

Answering whether faulty astrocytes affect healthy motor neurones

The next question that this research group wanted to answer was whether these faulty astrocytes had an effect on healthy motor neurones.

By growing faulty TDP-43 astrocytes with healthy motor neurones, the research group identified that the survival of motor neurones was not adversely affected.

This was surprising as other research groups have shown that when astrocytes have faults in the SOD1 gene (which cause one in five cases of MND with a family history) that motor neurones are compromised, even if the motor neurones were originally healthy.

TDP-43 is found within tangled lumps in over 90% of cases of MND (irrespective of whether it was caused by an inherited genetic mistake). However, when MND is caused by SOD1, TDP-43 is not found in these tangled lumps. This important difference could be leading to the key difference in whether astrocytes become toxic to contribute to causing MND.

These findings will of course need to be verified by an independent research group to determine that they are valid, but the results suggests that SOD1 and TDP-43 could be causing havoc in motor neurones in slightly different ways, both avenues leading to MND.

Our Director of Research Development, Dr Brian Dickie comments: “From a therapeutic perspective this is important because it means that specific treatments targeted at astrocytes may only be relevant and effective, in specific subsets of patients who will have to be carefully selected for drug trials.”

References:

Our news release on this finding.

March 2012 finding: Association-funded stem cell study achieves milestone

Serio A et al. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. PNAS 2013