How is tissue donation helping us to solve the MND puzzle?

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

Last year, I wrote about our trip to a brain bank. Here, we learned about how people can arrange to donate their tissue (brain and spinal cord) to tissue banks after they die, and how it is stored and used in MND research all around the UK.

What you might be asking is: what can tissue actually tell us about MND, and how will this help us find new treatments?

To find new drugs that can beat this disease we first need to understand what is going on in the brain, which is very difficult to study in living people. This is why post-mortem tissue from people with MND is an invaluable resource. Below are four reasons why tissue donation is so important. Continue reading

Focus on the research presented in posters in Dublin

Over 100 talks were given at this month’s International Symposium on ALS/MND in Dublin. There were also over 450 posters of research being presented too. Time in the conference programme was allocated on Wednesday and Thursday evening (day 1 and day 2 of the 3 day conference) to visit the posters – you might think that scheduled at the end of the day they would be less well attended – but not a bit of it! It was an extremely loud and buzzy part of the conference.

Below is a brief round-up of some of the posters that caught my eye. 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

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

Understanding and preventing the protein build-up that can cause nerve cells to die

Prior research has already shown that build-up of the protein TDP-43 is found in the majority of cases of MND (irrespective of whether it was caused by an inherited genetic mistake). In healthy nerve cells, TDP-43 is normally found in the cell nucleus (the management centre of the cell). But when we look at nerve cells from people with MND, we see that the TDP-43 has left the nucleus and moved to the main body of the cell and clumped together. We do not know why this happens, or how it leads to cell damage in MND.

In nerve cells, old proteins are ‘tagged’ for breaking down and disposal (or recycling). We have an idea that TDP-43 may impact on this process.

To investigate how TDP-43 causes motor neurones to die, Dr Jacqueline Mitchell and her team at King’s College, London have created several new mouse models to investigate how TDP-43 causes motor neurones to die in MND (our grant reference: 828-791). Continue reading

Using fruit flies to understand a genetic cause of MND

Mistakes in a gene known as ALS5, or spatacsin, cause a rare form of inherited MND that develops at a much earlier age than most other forms of the disease. Under supervision from Dr Cahir O’Kane, MND Association funded PhD student Alex Patto has been using fruit flies to understand how mistakes in spatacsin cause MND (our grant reference 861-792).

Prior to this research, which is based at the Department of Genetics at the University of Cambridge, nothing was known about how faulty spatacsin leads to motor neurone degeneration. Three and a half year years on, this research has shed light on this important question.

What did they find?

By conducting tests in the fruit flies, Alex has found that the spatacsin protein has a role in cell recycling (also known as autophagy), a process which keeps cells healthy. When the spatacsin protein is faulty it leads to disrupted cell recycling and abnormal levels of another protein called Rab7, which might contribute to MND development. Continue reading

Pesticides linked to increased risk of developing MND

The results from a study looking at the possible links between exposure to environmental toxins (found in pesticides) and motor neurone disease (MND) was published yesterday (9 May) in the journal JAMA Neurology.

A group of researchers from the University of Michigan, led by Dr Feng-Chiao Su and Dr Eva Feldman, have found that exposure to pesticides is associated with an increased risk of developing MND.

What did the study involve?

156 people with amyotrophic lateral sclerosis (ALS, a type of MND) and 129 healthy ‘control’ participants from Michigan, USA completed questionnaires on their occupation history, gave blood samples, or did both.

The questionnaire asked about their occupations over four windows of time; at any point during their life, in the last 10 years, in the last 10-30 years, and over 30 years ago. From their answers, the researchers worked out the likelihood of each participant’s exposure to pesticides.

The levels of 122 persistent environmental pollutants (including organochlorine pesticides or OCPs) were tested for in blood samples taken from participants.

Persistent environmental pollutants are those with a long half-life, meaning that they break down slowly. This meant that they could be tested for in the blood, even if exposure happened several years ago. However, the blood sample cannot tell us the source of the pollutants, such as if it was through work, at home or even from eating fruit and vegetables that had been sprayed with pesticides. Continue reading

The BMAA story in a nutshell

Research into the neurodegenerative condition known as Guam ALS-Parkinson Dementia Complex (ALS-PDC) has tended to find itself slightly isolated from the mainstream MND/ALS research world (‘isolated’ being a good word given that the location of the island itself) but I’ve had an interest since I was first introduced to the subject as a PhD student a quarter of a century ago.

This topic was raised once again on day one of the International Symposium on ALS/MND.

Guam map

So where exactly is Guam?

The Guam Story…

For those of you not familiar with this fascinating and convoluted story, the science writer Wendee Holtcamp has written an excellent article on the subject but in a nutshell (an ‘in joke’ for those who know the Guam story) the basis of the hypothesis is that a toxic molecule called BMAA (beta Methylamino-L-alanine) is produced by certain forms of blue-green algae. The theory goes that the residents of Guam for a while were exposed to higher than usual levels through their diet, which led to a high incidence of ALS-PDC on Guam in the 1950s and 1960s. Continue reading

Formaldehyde exposure and increased risk of developing MND

A new study published yesterday in the Journal of Neurology, Neurosurgery and Psychiatry (JNNP) highlights the link between increased exposure to formaldehyde and an increased risk of developing MND.

The study in the USA was conducted by Andrea Roberts and colleagues at the Department of Social and Behavioural Sciences at Harvard. They investigated whether a person’s exposure to formaldehyde in their occupation increased their risk of developing motor neurone disease (MND).20141020_MND Kings College_290

Formaldehyde is a colourless chemical that is used as a preservative in mortuaries, medical laboratories and by undertakers. Exposure occurs primarily by inhaling formaldehyde gas or vapour from the air or by absorbing liquids containing formaldehyde through the skin.

The study found that those with a ‘high intensity’ and probability of exposure to formaldehyde had nearly four times higher risk of developing MND compared to people who had no exposure to formaldehyde. All participants that fitted these criteria were funeral directors. The increased risk of developing MND in this occupation group was only found in men, with no link found for women.

Continue reading

Researchers identify the TBK1 gene as a risk factor in MND

recyclePublished on 19 February 2015 in the Journal Science, an international team of scientists have found mutations in the gene TBK1 as a contributory risk factor in MND.

Identifying TBK1

The majority of cases of MND are caused by a combination of subtle genetic, environmental and lifestyle factors. These subtle genetic factors in the majority of cases of MND (sometimes known as susceptibility genes) may increase someone’s risk of developing MND, but they do not solely cause the disease (they must be present in combination with a number of other factors in order to tip the balance for someone to develop MND). Find out more here.

Under the leadership of Dr Goldstein, based at Columbia University, the researchers have identified a new MND susceptibility gene – TBK1.  The researchers used whole genome sequencing to sequence the entire DNA of over 2,874 MND samples in America – you can find out more about this technique here. By screening a large number of samples, the researchers identified mutations in the TBK1 gene as a common subtle genetic factor involved in some cases of MND in America. Continue reading