News & Events
MND Association funded study finds new clues to genetic causes of MND
A study, part funded by the Motor Neurone Disease (MND) Association using money raised by Walk to d'feet MND*, and in collaboration with the ALS Association and other funding bodies, has found another genetic mistake that can cause a rare, inherited form of the disease.
This is the third MND Association co-funded research project that has resulted in the identification of a previously unknown genetic cause of MND.
The new research, published today in the journal Proceedings of the National Academy of Sciences, was led by Professor Jackie de Belleroche at Imperial College London. It suggests that mistakes (mutations) in a gene called ‘D-amino acid oxidase’ or ‘DAO’ for short, is the cause of MND in a family that is affected by a rare, inherited form of the disease.
By comparing these results to other families with the inherited form of MND as well as people with the sporadic form and people who do not have the disease, this specific genetic mutation could not be found. The results do however, provide further clues as to the possible underlying causes of all types of MND.
Dr Brian Dickie, director of research development at the MND, said: "Identifying definitive causes of MND, no matter how rare, is of vital importance. It will allow scientists to compare one form of MND with another, to more rapidly identify events that dictate whether a motor neurone lives or dies, no matter what the original cause of the disease is. It serves as a springboard for much greater understanding of MND - and it is through this understanding that effective treatments will be developed."
What does this research mean to somebody affected by MND?
Mutations in the DAO gene are extremely rare and so far, have only been identified in one family that is affected by the inherited form of MND.
This discovery will help us to glean a deeper understanding of what causes all types of MND. Investigators believe that discovering the genetic cause of familial MND will lead to a better understanding of what is going wrong in the more common, sporadic form of MND – as sporadic and familial MND are clinically indistinguishable, scientists believe that the mechanisms underlying both types of disease might be similar as well.
What did the researchers find goes wrong with DAO?
As well as finding that a mistake in the DAO gene (which holds the instructions for making the DAO protein) can cause a rare, inherited form of MND, the researchers also wanted to test what happens in cells when the DAO protein becomes faulty.
The results they found suggested that when faulty, DAO clumps together (aggregates) in neurones which may hold up the transport of materials around the cell. They also found that the cells with faulty DAO die in significantly higher numbers than those that were treated with the normal version of DAO.
On top of this, they also found that when faulty, DAO stops working correctly.
What does DAO do?
DAO normally breaks down a group of substances called ‘D-amino acids’, which play important roles in the everyday functioning of the human body.
When DAO is faulty, it can no longer break down these substances, which leads to an increase in their numbers. Interestingly, a specific type of D-amino acid called ‘D-serine’ has previously been found to accumulate in the spinal cord of people with the sporadic form of MND. This suggests that DAO, and its knock-on effects on D-serine may play a role in the development of the disease.
It is important to remember that we do not yet understand which of the above mechanisms can cause MND when DAO is faulty. More research is therefore needed to understand how DAO can cause MND.
How people with MND helped with this research
DNA samples were donated from people with the inherited form of MND, as well as people with the randomly occurring (sporadic) form of MND and controls who do not have the disease. These samples were used to compare and contrast the genetic codes held within the DNA to find that the DAO gene mistake was not discovered in anybody other than the affected family members.
If you are affected by MND and would like to know more about this research news, please contact our research development team on 01604 611880 or by email at research@mndassociation.org.
Contact:
01604 611843
louise.coxon@mndassociation.org
Notes to editors
*Walk to d'feet is a Trademark of The ALS Association and is used with permission.
