Researchers from the Flinders University, Australia and University of Miami have discovered a new protein that can act as a biomarker to track disease progression in people with MND. A paper written under the leadership of Dr Shepheard and Dr Rogers was published today in the research journal ‘Neurology’.
What is p75 and what do we know so far
The biomarker is a protein called p75, which initially
supports the growth of neurones during embryonic development and its levels markedly decrease after birth. Throughout our lives, p75 only reappears in higher levels when the body detects injury of the nervous system, and shows its presence in urine.
The researchers have previously shown that, after birth, mice with a mutation in the SOD1 gene, known to cause MND, had high levels of p75 after about 40 days from the onset of MND. This also coincided with increased levels of p75 in motor neurones found in tissue of people with MND after death.
What was the study about?
Following on from previous findings, samples of urine from 54 people with MND were compared to those from 45 healthy ‘control’ participants and levels of p75 protein were observed. The amount of p75 was significantly higher in people with MND compared to healthy controls; average levels of p75 were 5.6 versus 3.6 ng/mg creatinine, respectively (the levels of p75 were given as proportion of how much was in the urine to make comparisons between different samples easier to do).
As well as measuring p75 levels in each person once, the researchers made repeat measurements over time. Thirty one people with MND were followed up for up to 30 months and the levels of p75 were tracked. Their urine samples showed a stable increase of p75 levels by about 0.19 ng/mg creatinine per month. This means that the further the disease has progressed, the greater amount of p75 was found in the urine.
Why are these findings important?
Discovery of new biomarkers is one of the ultimate goals on our way to treat and beat MND. Knowing that the presence of a certain substance in the body is directly associated with a certain disease gives us an objective biological measure of the disease progression. This is crucial for clinical trials as the effects of new treatments can be measured by comparing the levels of biomarkers. Urinary p75 is an exciting new biomarker that can be used for MND research studies. It will be important to collect data on how levels of p75 change in larger numbers of people with MND over time, a work that is currently ongoing as a part of the CReATe consortium. You can find more information about the consortium on their dedicated webpages.
So far, progression of MND in clinical trials has been monitored by analysing patients’ blood and cerebrospinal fluid (‘cushioning’ fluid encasing the brain) or by observing their symptoms using the ALS-FRS questionnaire. A biomarker measureable in urine is easier to collect, and may mean that people with MND are more likely to take part in a clinical trial.
Note. ng/mg creatinine – measure of concentration of p75 in nanograms for 1 milligram of creatinine (a breakdown molecule present in urine)
Original research paper: Shepheard, S. R., Wuu, J., Cardoso, M, Wiklendt, L., Dinning, P., Chataway, T., Schultz, D., Benatar, M. and Rogers, M. (2017) Urinary p75. A prognostic, disease progression, and pharmacodynamic biomarker in ALS. Neurology, 88.