A Multicentre Biomarker Study in Neurodegeneration
Research type
Research Study
Full title
A Multicentre Biomarker Study in Neurodegeneration
IRAS ID
204405
Contact name
Heather House
Contact email
Sponsor organisation
University of Oxford
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
The purpose of this study is to investigate possible causes of damage to motor nerves in motor system disorders, in particular, Motor Neuron Disease (MND), and to find biological markers (biomarkers) of disease activity. We aim to obtain blood, cerebrospinal fluid, urine, and small skin samples from people with MND, people with other neurological conditions including disorders that mimic some of the symptoms of MND, and people who are neurologically healthy. We will then analyse these samples to look for genes and other biomarkers that can tell the difference between people with MND versus people without any neurological disorder, as well as between people with MND versus people with other disorders. We will also look for genes and other biomarkers that can predict how different symptoms will develop and how quickly this will happen. Identification of biomarkers that allow us to measure disease activity in MND and other neurological conditions can help speed up diagnosis, better predict how someone's symptoms will progress, better plan clinical trials of new treatments, and help understand the underlying causes of MND, related conditions, and other neurological disorders. Eventually, all of this knowledge may contribute towards the development of new treatments.
Lay Summary:
The study evaluated potential biomarkers from the biological samples of 258 people living with MND, 80 patients with other neurological conditions and 101 people who did not have a neurological condition, who were often the family and friends of the people living with MND who came to the clinic. There were a range of potential biomarkers investigated but we will only discuss the leading potential biomarker, known as neurofilament light chain (NfL).Neurofilaments form part of the internal scaffolding of nerve cells and are important in the maintenance of the axon, which is where electrical nerve impulses travel through. Motor neurones have the longest axons in the body, meaning they have the highest levels of neurofilaments. When motor neurones are dying these neurofilaments leak out and appear in the cerebrospinal fluid (CSF) and blood. NfL is now a well-known biomarker of nerve cell damage but is not specific for just MND as levels can be increased in a range of neurodegenerative conditions.
The study investigated both CSF and blood (plasma) NfL levels in all participants. They noted that NfL was found to reflect disease activity, meaning it mirrors the level at which the disease mechanisms for MND are active within the body. They also found that measuring CSF NfL did not provide any significant advantages over plasma NfL. This is advantageous to people living with MND, since blood tests for NfL are much more practical in a clinical setting, compared to measuring CSF which requires a lumbar puncture. This is made even more advantageous since the researchers noted that plasma NfL was strongly associated with survival and rate of disability progression, independent of any other factors that predict the likely course of the disease.
The study also found that plasma NfL was a potentially more sensitive reflection of the underlying disease process (i.e. what is happening at a biological level) than the measurement of ALSFRS-R, the current most common measure of disease progression for MND. This was suggested to be because NfL levels reflect disease activity over a narrow period of time whilst ALSFRS-R reflects disability progression that has built up over the time since the person living with MND has been diagnosed. This means that using plasma NfL measurements may have the potential to detect that the disease is slowing earlier compared to ALSFRS-R. Having a more sensitive measure is important since ALSFRS-R is a subjective measure of disease progression, dependent on the person’s opinion, honesty and how they feel on the day they are asked to complete it.
This research also went on to evaluate the performance of plasma NfL as a way to measure if a drug might be working in a clinical trial. The researchers conducted trial simulations based on the data collected during AMBRoSIA to model the inclusion of plasma NfL compared to ALSFRS-R. The simulation results showed that using plasma NfL over ALSFRS-R may help to detect treatment effects in smaller group sizes and more quickly, which in turn might mean that clinical trials could recruit a smaller number of participants and be able to build confidence in any likely benefit sooner. This would help prioritise only the most promising drugs for the larger studies needed to prove benefit fully.REC name
London - South East Research Ethics Committee
REC reference
16/LO/2136
Date of REC Opinion
24 Feb 2017
REC opinion
Further Information Favourable Opinion