Common Genetic Defects in ALS and Frontotemporal Dementia

New insights into Neurodegeneration

Some patients with either amyotrophic lateral sclerosis/motor neurone disease (MND) or frontotemporal dementia (FTD) carry the same rare genetic defects that cause other neurodegenerative diseases. These defects, known as “short tandem repeat expansions”, are the cause of more than 20 neurodegenerative diseases, including spinocerebellar ataxias and myotonic dystrophy.

A new study from Macquarie University, Australia, now suggests a common risk factor and mechanism that leads to neuronal cell death in several neurodegenerative diseases. This could lead to common therapeutic strategies in the future.

Most comprehensive study to date of specific gene defects in ALS and FTD

Researchers from the Macquarie University MND Research Centre and the Walter and Eliza Hall Institute of Medical Research identified the rare genetic defects in the genome of some people with non-inherited or sporadic ALS/motoneuron disease (MND) and frontotemporal dementia (FTD).

The study found that nearly 18% of sporadic ALS and FTD patients had DNA repeat expansion, which is thought to be involved in other degenerative diseases. The Australian study is the most comprehensive investigation of these gene defects in ALS and FTD patients worldwide to date.

Common risk factors for neuron death

ALS/MND leads to the death of neurons or motor nerves that connect the brain and spinal cord to the muscles. These are the cells that control our ability to move, breathe and swallow. The disease is progressive and eventually fatal.

Frontotemporal dementia (FTD) also causes neurons in parts of the brain to die, leading to a range of progressive symptoms including memory loss, unusual behaviour, personality changes and communication problems. It is the form of dementia recently diagnosed in actor Bruce Willis. FTD, unlike senile dementia, tends to affect mostly people under 65. The majority of cases of both conditions – about 90 per cent for MND and 60-70 per cent for FTD – manifest sporadically, with the remainder occurring in families.

Lyndal Henden, postdoctoral researcher at Macquarie University comments that the findings were a surprise: “The discovery of this genetic link between ALS and FTD provides a new opportunity to uncover common risk factors for neuron death and will have implications for understanding both diseases.”

Results could contribute to new therapeutic strategies

Study leader Kelly Williams, Associate Professor at Macquarie University, adds that while the team had suspected there might be overlap with other diseases, it was not to this extent.”Our findings suggest common risk factors in these diseases and common mechanisms that lead to nerve death. This may lead to common therapeutic strategies in the future. While the causes of sporadic ALS and FTD remain unknown. But this is an important step in the long-term effort to identify the risk factors for developing either of these diseases.”

The study, published in the latest issue of the journal Science Advances, is the culmination of 10 years of research that would not have been possible without the collaboration of patients with ALS or FTD who had provided biological DNA samples at both Macquarie University and the University of Sydney.