Clinical MS Research Group
Multiple Sclerosis, NMO and related conditions in Children
We are exploring changes in myelin and nerve health over time in children with demyelinating diseases such as MS. Our methods include electrophysiological assessment of the visual system as well as other visual parameters, in parallel with advanced MRI techniques. We are also investigating the utility of various blood biomarkers. Our goals is to establish the relationship between re-myelination and age in these conditions.
Children with MS
MS is rare in children and young people, but up to 5-10% of adults with MS are believed to have had onset of their first symptoms before the age of 16 years (and much more rarely before the age of around 10 years).
Paediatric-onset MS (PoMS) usually features more frequent MS 'attacks' (relapses) than adult-onset MS. Despite this, as well as often having a greater number of inflammatory MRI lesions, progression of symptoms in the years following diagnosis is usually slow. However, children and young people with MS typically go on to develop physical and cognitive impairments at a younger age than people with adult-onset MS.
We work closely with Paediatric Neuroimmunology team of Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust, which is one of the 8 hospitals in England specialising in children’s neuroinflammatory disease and PoMS.
ARMOUR: A study assessing remyelination in adults and children with central nervous system demyelinating diseases
Nerves in the brain and spinal cord are normally surrounded by a protective layer of a substance called myelin (similar to the plastic insulation of an electric cable). In multiple sclerosis (MS), and in other demyelinating conditions of the central nervous system (CNS), the immune system attacks the myelin, leaving nerve fibres (similar to the metal wire in the cable) unprotected. This causes nerves to malfunction, which can result in symptoms such as changes to vision, sensation, movement and cognition. Over time, unprotected nerve fibres die, leading to progressive disability.
To avoid this happening, we are trying to understand remyelination – the process by which myelin is regenerated – as this could reduce disability and prevent progression. At present, the tests employed for the diagnosis and monitoring of MS and other demyelinating conditions of the CNS are not sensitive to detecting the damage or the repair of damage (particularly standard MRI brain scans). Our study will therefore assess whether a combination of additional assessments (including specialised MRI scans, tests of the eyes, and blood tests) could be incorporated into routine clinical care for people living with MS.
The study is observational, does not change your regular care, and there are no risks from these specialised assessments. Participants will attend between 1 and 3 study visits over 12 months each lasting up to 3-4 hours. Remyelination is assessed by looking at the changes in eye tests and MRI brain scans between the initial and final visits.
The study is being conducted in Cambridge. Participants should have relapsing-remitting, primary progressive, or secondary progressive MS; myelin-oligodendroctye glycoprotrein antibody associated disease (MOGAD); or neuromyelitis optica spectrum disease (NMO). We are also seeking to recruit healthy volunteers to help us interpret our findings. There are no age limitations to recruitment, but participants will need to be able to cooperate with the eye tests and other investigations.
Further information is available from the study team:
Nick Cunniffe (Chief Investigator): ngc26@cam.ac.uk
Alasdair Coles (Co-Investigator): ajc1020@medschl.cam.ac.uk
Gioia Riboni-Verri (Co-Investigator): gr413@cam.ac.uk
MARMALADE-C: Multimodal Assessment of Re-Myelination And Long-chain neurofilament Assay following Demyelinating Events in Children is the name of the sub-study for children in the ARMOUR study
We are currently recruiting for a longitudinal observational study of myelin and axonal health in children (and adults) with MS and other demyelinating disorders, as well as healthy volunteers. In the study (IRAS 313164) participants attend for between 2-3 visits over the course of a year where they undergo specialised visual assessments and MRI, with the goal of establishing the feasibility of monitoring myelination and axonal health in clinical practice.
The main exclusion criteria for participation include being unable to tolerate an MRI scan, epilepsy, and taking medications which may affect the visual testing. There is no age limit, but participants need to be able to cooperate with the study assessments.
The study team are very happy to discuss any queries about the research; please contact:
Nick Cunniffe (Chief Investigator): ngc26@cam.ac.uk
Gioia-Riboni Verri (Co-Investigator): gr413@cam.ac.uk
Visual and MRI Outcome Development Program
Grounded in a firm understanding of disease biology, we use MRI and neuro-ophthalmological tools to identify new treatment targets, monitor subtle disease changes and detect whether experimental treatments are truly leading to repair.
SUB-PROJECTS
Using MRI to discover new treatment targets
Using MRI scans, we showed that in people with MS, brain tissue nearest the cerebrospinal fluid has the greatest damage (in lesions and outside of lesions). We proved that this is happening from the very earliest stage of the disease, is far better at predicting future relapses than traditional measures (brain lesions), occurs in all types of multiple sclerosis and can be reversed by using drugs which cannot get into the cerebrospinal fluid (and instead reduce immune cells in the blood). This all suggests that the underlying problem represents a novel treatment target - and increasing evidence supports our belief that this is coming from meningeal inflammation. See publications (Brain 2017 & 2021, MSJ 2020 x2).
New MRI trial outcome measures
Our first remyelination trial (CCMR1) included many 'firsts'. We showed that repair trials should examine grey matter lesions, not just white matter lesions (mirroring pathologists' findings of far greater remyelination in grey compared to white matter). We demonstrated that therapeutic remyelination can be detected in-vivo at the individual voxel level in white matter or grey matter lesions. And we showed that remyelination was impaired near cerebrospinal fluid. The resultant outcome measures are now being validated in other remyelination trial datasets and our current trial (CCMR2).
DANIEL-MS
A study examining eye movements in people with MS who have difficulty moving both their eyes in the same direction simultaneously due to demyelination in a key part of the brain. Learn more here.
Clinical trials in PoMS:
None currently open for recruitment.