MISL ProMS
Research type
Research Study
Full title
Molecular Imaging of Synaptic Loss in Primary and Secondary Progressive Multiple Sclerosis (MISL ProMS)
IRAS ID
273049
Contact name
Paul Matthews
Contact email
Sponsor organisation
Imperial College Joint Research Compliance Office
Duration of Study in the UK
2 years, 7 months, 0 days
Research summary
Research summary:
The purpose of this study is to explore the biology of progressive Multiple Sclerosis (pMS) to allow us to track how the disease develops over time. To do this, we will look at the concentration of a specific protein in the brain called SV2A using PET-MR imaging. SV2A is a marker of the number of synaptic connections in the brain. Synapses are special areas of the brain cell where they communicate with each other. Low synaptic connections in the brain is associated with a worsening of symptoms in MS. In this study we will be looking at measuring any changes in SV2A concentration using the radioligand [11C]UCB-J in the brain of patients with progressive MS over 12 months time. To achieve this aim, we will be using a PET-MR scanner which can perform a PET and MR scan at the same time. The information from the PET component will give us an indication on the concentration of the SV2A protein which is associate with the amount of connections of the brain cells. The MR component on the other end will tell us where those cells are located in the brain. The findings from this study will provide an understanding related to the biological signatures of progressive MS that will help us track the progression of the disorder. This information could help clinicians to offer the most appropriate therapeutic approach to their patients. We are aiming to recruit up to 16 participants with primary and secondary forms of progressive MS aged between 20 and 75. The study will be sponsored by Imperial College London.Lay summary of study results:
This study aimed to understand how progressive multiple sclerosis (proMS) impairs the principle points of connection between neurons in the brain, called synapses. Researchers used the positron emission tomography (PET) radioligand [11C]UCB-J in conjunction with 3T MRI to contrast synapse density and cortical thickness between people with proMS and age matched healthy volunteers, and to estimate rates of any progressive reductions in synapse number and density over time in the proMS group.The study involved 16 participants with proMS and a group of 13 healthy volunteers. People with proMS had two imaging sessions—one at the start and another approximately 16 months later—to observe any changes over time. The results showed that at baseline people with proMS had 15% lower [11C]UCB-J DVR-1 relative to matched controls in the thalamus, with smaller (non-significant) differences showing a similar relative trend across cortical regions. Over an average of 16 months, DVR-1 was further reduced between 5.5-7.0% in the hippocampus, parietal operculum and insular cortex with consistent smaller and non-significant trends in the same direction for other cortical and sub-cortical grey matter regions. Progressive reduction of the [11C]UCB-J DVR-1 was confirmed in volume corrected analyses, which suggested up to ~5% loss in the hippocampus over the average 16 month follow up. proMS also had smaller grey (18%) and white matter (10%) volumes than the matched controls. They show a generally consistent progressive loss of regional brain volume over the period of longitudinal follow up that was significant at about 2% for selective regions such as caudate, posterior cingulate, striatum, insula and precuneus.
We conclude from the study that synaptic connectors between neurons are lost with disease and continue to be lost over time. As these synapses are essential for information transfer in the brain, we conclude that their loss may be a mechanism of cognitive impairment in proMS.
REC name
London - Brent Research Ethics Committee
REC reference
20/LO/0103
Date of REC Opinion
21 Apr 2020
REC opinion
Further Information Favourable Opinion