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The growing importance of biomarkers

The growing importance of biomarkers

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This is blog number 15 in our ‘Symposium Blogathon’ – counting down to the 32nd International Symposium on ALS/MND. Numbers in bold green type correspond to the code in the abstract book. Click on the number to be redirected to the full abstract (the page may take a minute to load).

There is currently no diagnostic test for MND. Because of its relatively rare nature and non-specific symptoms, it is currently diagnosed by exclusion, whereby clinicians must rule out a whole range of other neurological and muscular conditions before giving a diagnosis of MND.

Finding a simple test that would make this process easier and faster would likely increase the effectiveness of existing and emerging treatments. These tests require searching for what is called a ‘biomarker’ – a signature of a biological change occurring in a specific disease (or a group of diseases). Some biomarkers have been identified for MND and are being tested to develop them into clinical tests.

Another reason to look for biomarkers is to keep track of the progression of the disease and predict survival. Researchers are now testing various measures to see how biomarkers might change as the disease progresses, and whether these differ in people with rapid progression from those with a slower progression rate. However, due to the current lack of biomarkers, measures of functional ability are used in clinics instead. While they are informative and provide us with a good estimate of disease progression, they are not as accurate as biological markers.

It is also recognised that the development and integration of objective markers of disease activity in MND is a key aim in advancing new drug development, as they can be used to track progression during clinical trials.

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Information Sheet
Biomarkers

Professor Robert Bowser is the Chief Scientific Officer, Professor and Chair of Neurobiology at the Barrow Neurological Institute in the USA. MND biomarker research has been ongoing for over 30 years. Biomarkers may be used to see how well the body responds to a treatment for a disease or condition and are increasingly used as a measurable outcome in clinical trials.

In his plenary talk ‘How important are biomarkers in drug development?’ (C19), Prof Bowser will discuss the growing importance of biomarkers in drug development, preclinical testing and human clinical trials; their use to identify MND at a pre-symptomatic phase and to monitor disease progression. There is little doubt that biomarker research has greatly accelerated MND drug development and has been a key factor in the expanding pipeline of MND clinical trials during the past decade.

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Video | 2018
Prof Martin Turner talks about the biomarker challenge

The neutrophil-to-lymphocyte ratio (NLR) is considered to be a valuable prognostic biomarker for predicting survival outcomes in many diseases. However, it remains unclear whether it can be used as a biomarker for MND. A team of researchers from China correlated NLR with disease progression and survival in 1,030 people with sporadic MND, who were assigned into three groups according to their NLR. Group 1 (n=544) had an NLR of less than 2, Group 2 (n=314) had an NLR between 2-3 and Group 3 (n=172) had an NLR of more than 3. Patients in Group 3 had a significantly older onset age, a lower ALSFRS-R score and a rapid disease course. Furthermore, faster disease progression was associated with higher NLR values. Compared to Groups 1 and 2, the survival time in Group 3 was significantly shorter. The NLR may help to predict the rate of disease progression and survival in people with sporadic MND (BIO-10).

The red cell distribution width (RDW) is a measure of the range of variation in red blood cell volume, and it has been reported to be positively correlated with inflammation and to be associated with a shorter survival in patients with lung disorders. Researchers in Portugal explored RDW as a potential biomarker in MND. Using data from 65 people with MND and 80 healthy controls, the researchers found the RDW value was significantly higher in people with MND. Having also assessed participants with MND by ALSFRS-R and forced vital capacity (FVC), they found that RDW did not correlate to ALSFRS-R scores but was significantly correlated with FVC. This suggests that RDW is a marker of respiratory function. Its value as a marker on survival and functional decline is still being analysed (BIO-20).

Researchers from Belgium compared markers of neurodegeneration (called NfL and pNfH) and markers of inflammation (called CHIT1, YKL-40 and MCP-1) as biomarkers of survival in cerebrospinal fluid (CSF) in 94 people with MND. They found that people with MND without pronounced neurodegeneration have a short survival in the presence of neuroinflammation, reflected by low NfL and high YKL-40 levels. This highlights the importance of CSF biomarkers to predict survival of people with MND and has implications for future sub-grouping of participants in clinical trials (BIO-28).

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Blog | 17 June 2020 | Research Dev Team
Identifying potential new biomarkers in the blood

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