Lithium revisited: Is there a baby in the bathwater?

At last year’s Airlie House workshop to develop new ALS/MND Clinical Trial Guidelines the focus was, of course, on MND, but there was also important input and learning from outside the field.

One of the most fascinating presentations was from an oncologist who was explaining how detailed genetic analysis of tumours was leading to an understanding of why some experimental cancer drugs appeared to only work in a small subgroup of patients. The take home message from the cancer field was that there should be more effort made in future MND trials to identify and analyse smaller subgroups of patients, in case a potentially positive effect might be missed.

A new research paper, published in the journal Neurology, raises some intriguing findings from the trials of the drug lithium that were carried out several years ago. Lithium generated a lot of excitement when researchers in Italy reported a positive effect of the drug in the SOD1 mouse model of MND. Almost as an afterthought, their research paper mentioned that they had tested the drug in a small short-term trial in patients and it appeared to have some effect. Continue reading

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

Families for the Treatment of Hereditary MND (FaTHoM)

Scientists from the University of Oxford have set up ‘Families for the Treatment of Hereditary MND’ (FaTHoM), an initiative to bring together the community of families affected by inherited forms of MND. Their first meeting will take place in Oxford on Tuesday 18th April.

Most people living with MND cannot identify a relative who has also had the condition. However, around 5% of people with MND will have a family history of the disease, which is known as inherited or familial MND. This happens when a single faulty gene is passed down from parents to their children across number of generations.

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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

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 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.

mine

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

Baking with proteins, mRNA and DNA

Today marks the start of MND Awareness month 2014 and our MND Research ‘blog a day’. Before we post our first guest blog we thought we’d set the scene by reminding you about genes and proteins.

As our fundraising campaign ‘Bake it!’ is back for 2014, we thought we’d re-blog our ‘baking with proteins, mRNA and DNA’ in order to help bake MND history!

Thank you for reading our ‘blog a day’ this Awareness Month. We would gratefully appreciate your thoughts and feedback via this short 2 minute survey.

MND Research Blog

Each and every one of us is made up of thousands of different ingredients, which all combine together to create something amazing; life. Perhaps the most important of these are proteins.

Each protein in the body has its own special job to do. From making our muscles contract to controlling blood sugar, proteins are an essential ingredient in life.

In MND research we have identified a number of MND causing genes. These are genes that are found to be mutated in some people living with MND, which somehow causes the motor neurones to die. But, how does this happen? How does a gene form a protein? This blog post explains how an MND causing gene becomes a protein.

As simple as baking a cake

Here at the MND Association we love our cake. So, I thought what better way is there to describe how we make proteins?

cheesecake cheesecake

Every cell…

View original post 631 more words

Same disease.. two very different mice!

The exact course, duration and rate of progression of MND often varies greatly from person to person; even when there is a known family history of the disease caused by a specific MND-causing gene (eg SOD1).

This same variability also occurs in mice. Researchers, funded by the MND Association, took two mice with the same SOD1 gene mutation from two different families (strains). By using these two mice the researchers identified a number of key changes in motor neurones that differ between fast and slow progressing forms of the disease.

Two mice… One gene

The SOD1 mouse

The SOD1 mouse model has been one of the most important MND research tools for scientists

Developing new disease models enables us to both understand the causes of MND and test potential new therapies.

Mice are commonly used in MND research and for the past 10 years or more, the SOD1 mouse model has been one of the most important research tools for scientists working in the field, particularly with testing potential new therapies.

Research published in September 2013 was carried out in a joint collaboration between Dr Caterina Bendotti (Mario Negri Institute for Pharmacological Research, Milan Italy) and Prof Pam Shaw (University of Sheffield, UK).

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