The gene abnormality behind the motor neuron disease has been identified in independent studies.
MND causes the death of motor nerves (neurons) that extend from the brain and spinal cord to all the muscles in the body, controlling the ability to move, breathe, eat, and drink. People with MND are gradually confined to a wheel chair, and breathing difficulties can follow. The disease can progress rapidly, with death typically 3 to 5 years after onset although there are long living exceptions.
AdvertisementAs per the study of Dr Ian Blair and Professor Garth Nicholson from the University of Sydney's ANZAC Research Institute, Australia, the gene now identified encodes a protein, called FUS, which is closely related to the function of another MND protein called TDP-43 (also discovered by the same research teams in 2008 to cause another form of motor neuron disease). Both these proteins slowly build up in neurons and eventually kill them to cause MND. For the first time, a common form of damage that kills motor neurons has been discovered. Until recently the cause of MND was unknown.
Families with inherited MND both in Australia and the UK co-operated in the study, and the paper has been published in the journal Science.
This is an important step towards developing effective screening and prevention for this fatal disease as well as finding treatments that prevent or reduce the inexorable progress of this so-far untreatable disease. Work can now commence to develop drugs that target the common damage mechanism aiming to prevent the fatal build up of these proteins.
A collaborative research project involving Professor Christopher Shaw of the Institute of Psychiatry, King's College London (KCL), Dr Tom Kwiatkowski at Massachusetts General Hospital (MGH) and Professor Robert H Brown at University of Massachusetts, had revealed similar findings last week.
This is the second gene to be discovered for MND (also known as Amyotrophic Lateral Sclerosis) in just one year.
Professor Christopher Shaw, senior author of the KCL paper, explained: "The new gene, called FUS, is a very important clue as to what causes motor neurons to degenerate. It links in with TDP-43, which is deposited in motor neurons in 90% of all people with MND.
"The genetic pieces of the jigsaw puzzle are beginning to fit together leading us in new and exciting directions of research. There are also major implications for diagnosis and treatment.
"We are very excited about this latest discovery and the collaboration between the Boston and London research groups has been crucial in this breakthrough. It is only by understanding the fundamental disease mechanisms that we will find a cure."
This latest discovery will not only help doctors to counsel those families at risk of MND but crucially aid researchers to develop better models of disease. The gene FUS is shown to be related to the TDP-43 gene found by Professor Shaw's team last year. Thanks to this development scientists now have two more genes with which to map out the origins of this dreadful disease and develop drugs to combat it.
This is the fourth MND-causing gene to be identified after 20 years of genetic research. The first gene, called SOD1, was discovered in 1993, the second ANG is a growth factor for nerve cells discovered in 2006. The new protein FUS has a very similar role to the third gene TDP-43, mutations in which were first described by Professor Shaw's group in 2008.
Research organisations including the ALS Association in the US and the MND Association in the UK contributed to the effort.
Commenting on this latest discovery, Dr Belinda Cupid, Research Manager at the MND Association said: "This is the second MND-causing gene to be identified in less than 12 months, a reflection of the accelerating pace of research around the world.
"Not only will it open up an entirely new avenue of scientific investigation, it will also allow researchers to compare the different known causes of MND and start to home in on the main biochemical events that cause motor neurones to die. This understanding will lead to new approaches to defeat this cruel disease."
The FUS protein, made by the FUS gene, normally carries out multiple functions within motor neurones. These include regulating how gene messages are created, modified, and transported in order to make proteins which are the building blocks of all cells.
The mutations were identified by detailed gene sequencing in families with an inherited form of the disease linked to Chromosone 16. Usually the FUS protein works in the cell's nucleus, but the mutation causes the protein to be abnormally located in the cell, outside the nucleus and it forms large aggregates within motor neurons in people carrying the mutations. More work is now needed to determine how the FUS and TDP-43 cause MND.