Motor neurone disease (MND) is rare but devastating, with patients slowly losing all their motor functions,such as walking, swallowing, and breathing, often dying within just 2.5 years following the onset of symptoms. MND diagnosis is currently plagued with elimination tests and sometimes unnecessary surgery. Researchers are hoping to change this by using cell-free DNA.
What is cell-free DNA?
Cell-free DNA circulates in our blood, as opposed to being wrapped up in the nucleus of a cell, Dr Fleur Garton from IMB explains.
“As our cells renew themselves, the contents from dead cells are broken down, recycled and short fragments of DNA end up in our blood,” Dr Garton says.
“Our cells are always turning over so we all have cell-free DNA circulating, but your levels can change if you’re pregnant, or if you have a tumour – so it can be a reflection of what’s going on in your body at any time.”
Cell-free DNA has already been harnessed for non-invasive prenatal tests (NIPTs) and liquid biopsies that test for cancer.
Using cell-free DNA to research MND
The success of these tests and readily available technology spurred Dr Garton and collaborators from the University of California to investigate using cell-free DNA to progress research into MND.
“The fact that tests using cell-free DNA are already in the clinic removes a lot of barriers to translation – it’s already been shown that it’s accurate, efficient and economical,” Dr Garton says.
“We hypothesised that MND patients have an increased cell turnover and high levels of cell-free DNA in the blood, and we found this was true.
“But it’s not as straightforward as ‘a high level of cell-free DNA is bad’, as your levels can fluctuate with exercise or after fighting off a virus.
“We were really keen to try to understand what cells these fragments were coming from, so we measured the methylation of cell-free DNA.”
A chemical clue
Methylation is one way in which gene activity is controlled and occurs when a chemical called a methyl group is added to DNA.
“Some methylation patterns are highly conserved across cell types, so we can look at methylation on DNA fragments and make an informed guess on which cell the DNA has come from.”
Dr Garton and collaborators developed a method to estimate from where the DNA originated. While typically this is from blood cells, an increased proportion of the cell-free DNA in MND patients came from skeletal muscle, which is affected by the disease.
“We are now looking at the methylation status of cell-free DNA in a much larger number of blood samples and types of neurological conditions, generating data that will bring us closer to a sensitive test for MND.
“Our ultimate goal is a simple blood test to diagnose MND and track disease progression, which would be particularly useful whilst trialling new treatments.”
A personal motivation
Dr Garton is driven by the need to develop better outcomes for MND by a deeply personal reason.
“My brother needs lifelong care due to a condition that is similar to MND,” she says.
I’ve made it my life’s mission to carry out research that will make a difference to those who have these diagnoses.”
“I want others to be able to live life to the full and have every opportunity they deserve.”
Dr Fleur Garton
