Causes

The MND Association funds a number of research projects into the causes of MND.

Identifying causes of MND

These projects aim to understand the causes of motor neurone degeneration. This is essential to allow the development of treatments. Only by understanding what goes wrong in MND can scientists know how to design and where to target drug treatments. A selection of our newest causes projects are highlighted below:

Download our Research we fund information sheet for details of all of the projects we fund.

“Hearing the latest results from the lab is what gets me out of bed every morning. We need to find out what causes motor neurone degeneration if we are to cure MND”

– Prof Chris Shaw, King’s College London

A selection of some of the research we are funding into the causes of MND:

Investigating jumping DNA as a genetic risk factor for MND
  • Prof John Quinn, Dr Gerald Schumann, Dr Vivian Bubb, Dr Gerome Breen and Prof Ammar Al-Chalabi
  • University of Liverpool, Paul Ehrlich Institute and King’s College London
  • £204,435 (Biomedical project) over 3 years
  • Start date: November 2015
  • Our Ref: 843-791

The majority of cases of MND are believed to be caused by a combination of subtle genetic, lifestyle and environmental factors. This project aims to identify whether ‘re-shuffling’ of DNA in the very early embryo might be
responsible for events later in life.

By using brain tissue and genetic data already available the group will use powerful computers to look for evidence of this re-shuffling through the identification of stretches of DNA known as ‘retrotransposons’ or ‘jumping DNA’.

The function of C9ORF72 in MND
  • Prof Chris Miller and Dr Wendy Noble
  • King’s College London
  • £94,051 (PhD Studentship) over 3 years (+10 months extension)
  • Start date: October 2013
  • Our Ref: 863-792

In 2011 mistakes in the gene C9ORF72 were identified as the most common cause of inherited MND. Since then, researchers from around the world have been trying to find a way to open-up and reveal more about this MND-causing gene.

The aim of this research project is to gain insight into the function of the C9ORF72 protein (made by the C9ORF72 gene). Specifically, the researchers will use advanced microscopy to find the location of C9ORF72 within cells, investigate the consequences of varying the amount of the C9ORF72 protein produced on overall function of motor neurones, and investigate whether C9ORF72 is involved in a specific process called ‘transcription’.

Update: PhD student Ambra Annibali has successfully created a new antibody for detecting the C9ORF72 protein. She hopes to use this to determine where the C9ORF72 protein is found within the motor neurones and how this protein may cause MND in some individuals.

Understanding the role of Calcyclin in developing MND and Alzheimer’s disease
  • Dr Bradley Smith, Dr Salvatore Adinolfi and Prof Corinne Houart
  • King’s College London
  • £95,746 (PhD studentship) over 3 years
  • Start date: October 2017
  • Our Ref: 888-792

The grantees have recently found that mutations in the ANXA11 gene are responsible for approximately 1% of all cases of MND. In looking at how ANXA11 mutations cause motor neurones to die, they have highlighted damage to a protein called calcyclin. Little is known about whether calcyclin causes motor neurones to die in MND or whether it has been ‘caught up in the cross fire’ of other damaging effects.

This research project will investigate the role of calcyclin in MND in more detail in order to understand more about the shape and chemistry of the protein and where it is found in people with MND. They will do so by using post-mortem tissue from people who donated their brain and spinal cord for research and by modelling the function of calcyclin in a zebrafish model of MND.

Gene-Environment database and analysis system
  • Prof Ammar Al-Chalabi and Dr Richard Dobson
  • King’s College London
  • £171,478 (Biomedical project) over three years
  •  Start date: March 2016
  •  Our Ref: 829-791

Genetic research into MND generates huge amounts of data. This project is a collaboration between MND researchers and bioinformaticians (those with expertise in computing, statistics and biology). The aim is to develop a system that will let researchers easily share genetic, clinical and epidemiological information, as well as adding new information as it becomes available.
The resource will speed up the identification of genetic factors involved in MND, but will also serve as a platform for unpicking genetic, lifestyle and environmental interactions.

The role of glycospingo-lipids in MND
  • Prof Frances Platt and Dr David Priestman
  • University of Oxford
  • £96,252 (PhD studentship) over 3 years
  • Start date: October 2016
  • Our Ref: 883-792

There is an unexplored link between MND and rare diseases called lysosomal storage diseases. Lysosomes are a part of the cell where larger molecules, no longer required, are broken down for ‘recycling and disposal’. One type of molecule that the lysosomes break down are glycosphingo-lipids (GSLs). The team has recently found a link between GSLs and MND.

This project will investigate the role of a specific GSL in MND, using patient blood samples, cell lines and post-mortem tissues, as well as various samples from mouse models. The team will also test whether they can delay MND progression by targeting GSLs with therapies. This study will open up a new perspective on MND and could lead to new directions for MND research and therapies.

Identifying changes in the brain tissue in MND and FTD
  • Dr Olaf Ansorge and Prof Kevin Talbot
  • University of Oxford
  • £96,892 (PhD studentship) over three years
  • Start date: October 2015
  • Our Ref: 877-792

Some people with MND will also develop frontotemporal dementia (FTD), this means that cells in several parts of the brain are affected. Commonly these people will carry a gene mutation known as C9orf72. In some people with C9orf72 gene mutation, they will develop only MND, other people with the same mutation will only develop FTD and some people will develop both conditions.

Looking at post-mortem brain tissue down the microscope, there are three typical signs that cells are affected. They will either see tangled TDP43 protein, a tiny fragment of C9orf72 protein or a clump of C9orf72 RNA. Using brain tissue from the Oxford Brain Bank, Dr Ansorge and Prof Talbot aim to identify which brain cells are most susceptible and whether there is genetic variation within specific regions of the brain that could help explain the differences between the two diseases.

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