Histological analysis of fixed human post-mortem brain tissue sections
Research type
Research Study
Full title
Cell type specific spatial mapping of mRNA and proteins in amyotrophic lateral sclerosis
IRAS ID
302165
Contact name
Andras Lakatos
Contact email
Sponsor organisation
University of Cambridge
Clinicaltrials.gov Identifier
MR/P008658/1, Continuation of MRC grant
Duration of Study in the UK
0 years, 7 months, 1 days
Research summary
WHY?
Amyotrophic lateral sclerosis (ALS) is a common type of rapidly progressive motor neuron disease, affecting nerve cells, the neurons in the brain and the spinal cord leading to muscle weakness and dementia. It is fatal, untreatable and affects about 5000 people in the UK at any time. The overarching aim of this study is to explore the molecular changes in precise detail in various cell types in the brain of patients with ALS that can overlap with frontotemporal dementia (FTD). In order to develop successful therapies we need to understand not only the problems occurring in neurons but also in non-neuronal cells, the glial cells that emerge as key players contributing to disease in ALS.WHAT?
We will specifically examine the level and distribution of molecules with major glial cell types, the astrocytes, which can harm neurons in ALS/FTD. These are proteins or molecules that code them, called messenger-RNA (mRNA) which can be visualised in brain tissue sections derived from preserved non-live samples of deceased patients. The combination of this approach with our ongoing investigations of astrocyte-neuron interactions in the culture dish are powerful tools for revealing potential treatments targets.WHO?
The anonymised brain samples will derive from deceased patients affected by genetic mutations causing common cell disturbances in ALS and also from patients with non-neurological disease.WHERE AND HOW?
Samples will be provided by the Cambridge Brain Bank (CBB), from which histological sections will be made in the Centre for Brain Repair (CBR), University of Cambridge. The analysis will take place in the CBR with assistance of our collaborators (Prof. Long Cai, Caltech). The project will provide an unprecedented opportunity to inform desperately needed ALS drug-developments.REC name
London - Camden & Kings Cross Research Ethics Committee
REC reference
21/PR/1304
Date of REC Opinion
17 Sep 2021
REC opinion
Favourable Opinion