ANXA11 – another gene closer to understanding ALS

A new research paper has been published today in the Science Translational Medicine journal, describing a new gene implicated in developing MND. What is this gene and why is it important for our fight against MND?

Although they are not the sole cause of MND, genes play a big role in someone’s probability of developing the disease. A number of such genes that make a person susceptible to developing MND have already been identified, with most of them causing the rarer, inherited form of the disease.

A new addition to a list of genes that are related to development of ALS, the most common form of MND, has been discovered by researchers from King’s College London. Dr Bradley Smith and colleagues screened genetic data of an unusually high number of people of European origin: 751 with inherited – familial – ALS (fALS) and 180 with non-inherited – sporadic – ALS (sALS). Detailed analysis of this data found that specific mutations in the ANXA11 gene are associated with around 1% of all fALS and 1.7% of all sALS cases. 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

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

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

More clues to the inner workings of the C9orf72 gene

Continuing the ‘gene hunting theme’ on from our last blog post on Project MinE, a recently published study has shed more light on the C9orf72 gene mutation.

The C9orf72 gene mutation is the most common cause of the rare inherited form of MND (about 40% of all people with inherited MND have this mutation). Some people with the sporadic form of MND also have this mutation, and it has been linked to the development of a type of dementia called frontotemporal dementia (FTD).

Figuring out the normal function of C9orf72

A study by Jacqueline O’Rourke and colleagues at Cedars-Sinai Medical Centre in Los Angeles used mice that lacked the equivalent gene to C9orf72.

When this gene was absent, the mice developed normally and their motor nerve cells were unaffected.

From this evidence they discounted one of theories about the C9orf72 mutation – that a change to the gene stops it working entirely and that this affects the health of motor neurons. Continue reading

Looking for MND genes: Project MinE update

Project MinE is an international genetics project that is analysing DNA from people with MND in detail.

For the majority of people with MND, the disease appears ‘sporadically’ for no apparent reason. For a small number of people, approximately 5-10% of those with MND there is an inherited link, in other words the disease runs in their families.

We know a lot about the genes that are damaged in the rare inherited forms of MND. We also know that very subtle genetic factors, together with environmental and lifestyle factors contribute to why the majority of people develop the disease. These subtle genetic factors are very hard to find.

The goal of Project MinE is to find the other genes that cause inherited MND and help us find out more about these subtle genetic risk factors.

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Project MinE was born when Dutch entrepreneur Bernard Muller challenged his neurologist to do something with all the DNA samples in his freezer – samples being stored there for future analysis. ‘Why can’t those samples be analysed now?’ was his question. That was two years ago! Continue reading

“To test or not to test”, that is the question

A huge ‘atlas’ mapping the locations of motor neurone disease (MND) causing mutations within the genetic code has been collated. This has followed years of genetic analysis and sequencing of the DNA of people with MND, and their family members.

The people who have given their time and DNA have played a hugely important part in helping researchers learn more about MND, particularly the inherited form of the disease. Dr Benatar, who spoke in this session highlighted “there is a desire and interest by people who may have inherited MND to contribute to research into this disease, if not for their benefit then for the benefit to future generations of their family“.

The first session on day two of the Symposium looked at the topic of genetic testing and counselling. All the presentations had a common theme of this topic being a two-way street – after all the help people with MND and their families have given to help with research, now research efforts have been focussing on the ways to better help those who decide to have genetic testing for inherited/familial MND. Continue reading

New ALS gene represents another small step

It wouldn’t be the Symposium without a new gene discovery.

Although technology has allowed incredible advances in the gene-hunting field, this is countered by the fact that as more and more familial amyotrophic lateral sclerosis (FALS) genes are found, it makes the search for the remaining unknown genes harder  This is in part due to the fact that the undiscovered genes are likely to be increasingly rare (so even more rigorous detective work is needed) but the challenge is compounded by the fact that there are fewer and fewer samples with an unknown cause available each time a new gene is found.

The solution to these problems lies with greater collaboration, sharing knowledge, expertise and of course the vital samples needed for the research to happen.Dr Brad Smith

Dr Brad Smith (King’s College London) unveiled the latest collaborative effort, involving over 50 researchers across 9 countries. The researchers took an approach called Exome Sequencing, which analyses the 1% of the genetic code where most mutations are likely to be found, to look for genes in several hundred FALS cases where the genetic cause was still unknown. They then compared their findings with those from 60,000 individuals in publicly available databases. Continue reading

The TBK1 jigsaw puzzle

samplesFollowing on from the identification of the gene TBK1 as a contributory risk factor for MND in February, the plot thickens further with research published yesterday by Dr Jochen Weishaupt and colleagues.

Published in Nature Neuroscience, the team found mutations in the TBK1 gene as a cause of both inherited MND and frontotemporal dementia in Germany and Sweden. Continue reading

The power of a blot!

During December and November the Research Development team receive a number of Christmas presents from our funded researchers. These presents come in the form of ‘annual reports’ and, although they may not be wrapped in Christmas paper, once you open them you’re sure to find a nice research surprise!

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One of our PhD students, Ambra Annibali, under the leadership of Prof Chris Miller at King’s College London, shared with us a lovely gel image in their report. The ‘gel image’ in this case is what researchers call a Western Blot.

Continue reading