What goes wrong with electrical signalling in MND?

Last year, we introduced a PhD Studentship that we are funding at the University of St Andrews. Under the supervision of Dr Gareth Miles and Prof Siddharthan Chandran, the student working on this project, Amit Chouhan, is investigating why electrical signalling goes wrong in MND.

As the project enters its second year, Amit and the team have made some important discoveries… Continue reading

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. 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

The role of the protein TDP-43 in MND due to C9orf72 mutations

Mistakes in the C9orf72 gene are the most common cause of inherited MND, and can be linked to about 40% of all cases. Now that we know that damage to the C9orf72 gene causes MND the next step is to understand how this mutation causes the motor neurones to die. In particular Dr Jakub Scaber is looking at how another cause of MND – the formation of clumps of protein called TDP-43 are linked to changes to C9orf72. (You can read more about TDP-43 in the post about Dr Mitchell’s project yesterday).

Jakub Scaber

Dr Jakub Scaber, University of Oxford

Dr Jakub Scaber is a MND Association/ MRC Lady Edith Wolfson Clinical Research Fellow at the University of Oxford, he is studying how mistakes in the C9orf72 gene and TDP-43 protein cause MND (our grant reference: 945-795).

These fellowships are jointly funded by the Association and the Medical Research Council (MRC). They support clinicians (practising doctors) wishing to pursue scientific research and aim to strengthen the links between laboratory and clinic. Our financial commitment to these fellowships varies between £86,000 and £280,000 for up to five years. For this project the total cost of the grant is £173,697 and the MND Association contributes £86,848 with the MRC paying the rest of the money. 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

Buckets more research – some of our plans for the Ice Bucket Challenge money

Today’s announcement of the difference the ALS / MND ice bucket challenge has made included a number of areas of research investment. You’ll be hearing much more about these as our plans develop, but here are three examples to give you a flavour of things to come.

ibc oxford

Oxford researchers get an icing!

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Measuring the nerve impulse

Devlin et al (2015)

Researchers identify that loss of nerve signalling may be an early sign of MND

Published in Nature Communications on 12 January 2015, Association-funded PhD student Anna-Claire Devlin, based at the University of St Andrews, has identified that loss of nerve signalling may be an early sign of MND.

Under the leadership of Dr Gareth Miles and Prof Siddharthan Chandran (University of Edinburgh), Anna-Claire measured the nerve impulses in stem cell derived human motor neurones and identified that the ability to send a nerve impulse is impaired during the early stages of the disease. Continue reading

Our DNA Bank: the times they are a changing..

DNABankLogoThis autumn sees an exciting new development in the MND Association’s DNA Bank. Researchers can now use the samples within it to understand why motor neurones die as well as what the triggers are for MND.

How the DNA Bank began

Beginning in 2003 and running until 2012, approximately 1,500 people with MND, 1,000 healthy ‘controls’ – often the partner or spouse of someone with MND – and a further 500 members of families affected by MND gave a blood sample to help researchers understand more about the genetic causes of MND.

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Using induced pluripotent stem cells to further our understanding of MND

Dr Jakub Scaber from the University of Oxford is our newest Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Clinical Research Fellow. He is investigating how the newly identified C9orf72 gene causes MND in some individuals using induced pluripotent stem (iPS) cell technology.

Courtesy of Prof Chandran's laboratory, University of Edinburgh

Courtesy of Prof Chandran’s laboratory, University of Edinburgh

Researchers funded by the Association were amongst the first to create human motor neurones from donor skin cells, mimicking the signs of MND. Today, the Association is committed to funding six research projects using iPS cell technology to further our understanding of MND. This includes the recently awarded fellowship to Dr Scaber. Read more about these projects here.

Dr Scaber will be using iPS cell technology to take skin cells from someone living with the rare inherited form of MND (5 – 10% total MND cases) caused by the C9orf72 mutation. Similar to Prof Chandran’s research at the University of Edinburgh, he will then make these cells ‘forget’ what they are and turn them into motor neurones. By studying these cells in detail he aims to find out how this mutation causes MND and whether or not gene therapy can be used as a potential treatment.

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The cell that never grew up

With Pantomime season kicking off back home in the UK, delegates in Milan were introduced to one of the newest cellular villains in the MND story – oligodendrocytes.

Although oligodendrocytes were first identified in the 1920s and are known to be affected in multiple sclerosis, they were generally considered as ‘bit part’ players in MND rather than ‘centre stage’.

All that has started to change in the past couple of years, with researchers in the USA and Belgium independently showing that, in both SOD1 mice and human post mortem MND brain tissue, the brain was making new oligodendrocytes to replace ones that appeared to be dying off.  The problem is that the new ones being formed appear to get stuck in an immature state and therefore do not perform their role of helping motor neurons to maintain appropriate energy levels and also send electrical signals down their long nerve fibres.

So, by getting stuck in a ‘Peter Pan’ scenario of never growing up, oligodendrocytes may be at best, unable to help protect the death of motor neurons or, at worst, they may actually contribute to the degeneration. Peter Pan rather than Captain Hook as the pantomime villain is a novel twist to the script!

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