Amongst the heavy hitters that includes fingolimod, alemtuzumab, natalizumab and ocrelizumab, the ultimate measure of treatment effectiveness is their ability to protect brain volume loss. The release of axonal proteins, including neurofilaments, have been demonstrated to closely emulate this slow brain volume loss that we see in MS (Figure 1).
(A) BPF change at 1 year. (B) PBVC at 1 year. (C) BPF change at 5 years. (D) PBVC at 5 years. BPF = brain parenchymal fraction; NfL = neurofilament light chain; PBVC = percentage brain volume change. Arrambide G et al. Neurology 2016 87(11)
Through our study of neurofilaments, we have learnt that neuronal injury is present very early on in the MS disease process, even when asymptomatic (i.e. as incidental MRI head findings in those not yet diagnosed, Figure 2), and of course relapses are fundamental in the early damage that occurs in MS.
Figure 2: Kaplan-Meier curves for time to CIS and time to multiple sclerosis in RIS patients according to high and low CSF CHI3L1 (A) and NfL levels (B) and (C) positive and negative oligoclonal bands.
But evidence is important, and to date fingolimod, natalizumab and ocrelizumab have all demonstrated an uncanny ability to reduce CSF (cerebrospinal fluid) levels of neurofilaments in MS. The new kid on the lock ocrelizumab manages this in a stupendous three months (OBOE study). The question on whether alemtuzumab achieves a similar status as it’s partners is unanswered.
At the 2018 ECTRIMS we saw that alemtuzumab leads to sustained reduction in the rate of brain volume loss in RRMS (see earlier blog post), despite being only given as two courses in more than half of those receiving it. So one might predict that we should note a drop in CSF levels at year 1 and year 2, from the start of treatment. And this is what we have set out to do as part of a Barts MS study led by myself to see if this true. Currently, this study is open only to those living within commuter distance of the Royal London Hospital, UK. UMass, Massachusetts will also be partnering with us shortly.
The eligibility criteria for this study are as follows:
Inclusion criteria –
1. Diagnosis of relapsing-remitting MS
2. Age 18-55y
3. EDSS score between 0-5.5
4. Commencing alemtuzumab therapy
1. A diagnosis of secondary progressive MS or other forms of progressive MS
2. Those unable to comply with study requirement.
1. Lumbar punctures for CSF NfL at Time 0, Year 1 and Year 2 with paired blood samples.
2. Blood, urine and stool tests (this is to study the gut microbiota).
3. Brain MRI scans at Time 0, Year 1 and Year 2.
If you are interested in participating please inform your Neurologist of this study.
It is registered on Clinical Trials.gov; and contact details can be found there.
CoI: This study is funded by Sanofi-Genzyme but is an Investigator Led Trial sponsored by Queen Mary University of London.