MIND-MAPS-ALS
Research type
Research Study
Full title
Molecular Imaging of Neurodegenerative Disease – Mitochondria, Associated Proteins & Synapses – Amyotrophic Lateral Sclerosis
IRAS ID
259539
Contact name
Marios Politis
Contact email
Duration of Study in the UK
2 years, 0 months, 30 days
Research summary
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neurone disease. In this disease there is death of the nerve cells that control muscle movement. This leads to increasing muscle weakness, including muscles important for movement, swallowing and breathing.
The cause of this condition is still unknown, although it is thought that people’s genes and their environment play a role. Our aim is to look into the cause of this disease, so that in the future treatments can be made to slow or even stop the worsening of the condition.
We plan to use a special type of brain scan, called PET, to explore how brain activity is effected in ALS. In particular, we will measure the mitochondrial activity (the source of energy of brain cells) and synapses (the links between the nerve cells that allow communication and control of the movements). Another type of brain scan, called MRI, will be used to investigate the brain’s structure and function. Finally, we will complete a detailed clinical and psychological assessment.
We aim to follow up participants with a new ALS diagnosis (with symptoms starting in their limbs), aged between 25 and 85, over a one year period. Three clinical visits will take place at King’s College Hospital and four visits for brain scans will take place at Invicro (an imaging centre next to Hammersmith Hospital). We will reimburse transportation to and from home to the hospital and refreshments throughout the visits. We will also offer, as a small thank you, £100 per scan (up to £800).
The findings from this study will be reported at local, national and international meetings and conferences. We will maintain a high impact publishing policy, submitting to open-access, top-tier, and peer-reviewed journals and will inform participants of relevant publications.Summary of research
The main objective of this research was to study, in a group of people with Amyotrophic Lateral Sclerosis (ALS), how some parts of the brain cells (named synapses and mitochondria) are altered. We can do this thanks to a special scan named Positron Emission Tomography (PET) which uses specific molecules named tracers to selectively study a protein, or a cellular function. We have used three PET tracers named [11C]UCB-J, [11C]SA4503, and [18F]BCPP-EF, to study the mitochondria and the synapses of people with ALS.
We have recruited 16 people with ALS focusing on some specific characteristics: they had a form of disease named “spinal-onset” which means that their symptoms have started, and mainly affect, the arms and legs. All participants underwent a clinical visit with some tests to understand the presence and extent of their symptoms, focusing on how they move, their level of autonomy in everyday tasks, and how is their memory, attention, and generally the way they think and behave.
They therefore underwent the three PET scans, and a Magnetic Resonance Imaging (MRI) scan, on different days. They were also invited to repeat some of these activities (namely, the clinical visit, the MRI scan, and the PET scan with [11C]UCB-J only) after approximately six months, and approximately 12 months from the baseline visit. We had a very good retention to the study: 15 participants took part to the six-month follow-up, and 13 took part to the 12-month follow-up.
The data collected from the patients has been compared with a group of healthy controls of similar age, who underwent the scans in the past as part of previous studies. The study is part of a large academic-commercial programme called MIND MAPS (Molecular Imaging of Neurodegenerative Diseases – Mitochondria, Associated Proteins, and Synapses).
We have subdivided the analysis in baseline and follow-up. At baseline, we have noted that the patients with ALS had a generally lower uptake of the tracer [18F]BCPP-EF, testing for the function of the mitochondria, and this was severely decreased in those showing a fast progression of their symptoms. In these patients, the decrease of [18F]BCPP-EF in several important brain regions was correlated with the severity of their symptoms as measured with a widely used clinical scale of ALS, named ALSFRS-R. This subgroup of patients also showed a decrease in the uptake of the tracer [11C[SA4503, testing for the levels of a protein, named sigma-1 receptor, that is located close to the mitochondria. This means that, a derangement of how mitochondria and its associated proteins work may be altered at least in people with ALS who progress fast with their symptoms. The mitochondria are essential for the production of much needed energy for the brain. A loss of energy may drive some of the alterations we see in people with ALS. We have recently published this work in a peer-reviewed journal named Neurobiology of Disease. The link to the article is available here https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.sciencedirect.com%252Fscience%252Farticle%252Fpii%252FS0969996125003559%253Fvia%25253Dihub%2FNBTI%2FcCTCAQ%2FAQ%2Fb37d589c-851c-4785-866e-38f6b1679ded%2F1%2FhK6re3nxPT&data=05%7C02%7Cbromley.rec%40hra.nhs.uk%7Cee33538527c14a49e28a08de3ef18f27%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639017404372383592%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=q7dFtXzUy%2FjPbWOSshWfer3N2maWSrPDNtf17l3UouI%3D&reserved=0 and can be accessed in open access mode.
We are currently analysing the data from the follow-up analysis. This analysis is interesting because a decrease of the brain uptake of [11C]UCB-J, testing for the density of the synapses, has been noted in several other neurological conditions such as Parkinson’s disease and Alzheimer’s disease, among others. Often, but not always, this has been associated with a decline of cognitive abilities. This is important because the synapses are the structures the brain cells use to communicate with each other hence fewer synapses may impact the way we remember things, or pay attention, etc. We hope to publish the results of the follow-up analysis very soon.REC name
London - Bromley Research Ethics Committee
REC reference
19/LO/0779
Date of REC Opinion
24 Jun 2019
REC opinion
Further Information Favourable Opinion