Workstream 3
Nested Biomarker Development Studies
Lead Sites for Workstream 3
Aims and Objectives of Workstream 3
Aim: To study the changes of the molecular environment in biofluids that occur with disease progression, in parallel with alterations observed in NfL concentration. To this end, we will study clinically well-characterised longitudinal cohorts spanning the disease natural history to identify meaningful proxies of disease activity and treatment response, in the form of trajectories of biomarkers that change with rate of disease progression and with treatment.
Primary objectives:
Unbiased identification of additional biomarkers of prognosis using NFL trajectories and risk scores as proxies of predicted outcomes.
Targeted analyses of markers associated with immune dysregulation and dysmetabolism.
Genotype and phenotype correlations in the trial populations with different NFL trajectories to support biomarkers discovery.
Identify IMP-specific changes in the biofluids proteome that inform target engagement.
Secondary objective:
Work towards integrated into the broader UK MND Research Institute (MNDRI) initiative to create a national clinical data and biological samples repository through NIHR and Telehealth in MND (TiM) platforms.
What are Omics?
Omics is a term used to describe the field of study relating to the analysis of large datasets obtained from a cell, individual or other specified region. Members of this group are recognised by the suffix “ome” and include:
genome: DNA sequences
exome: the DNA sequence of all the exons in a genome
epigenome: chemical modifications to DNA and DNA-associated proteins
transcriptome: RNA sequences
proteome: all of the expressed proteins
metabolome: all of the expressed metabolites
microbiome: genomic sequences of all the microbes inhabiting a bodily system
As part of EXPERTS-ALS, we will collect blood, stool and urine samples from participants and perform omics studies on them to try to better understand ALS, the drugs we are testing, and why certain people may or may not respond to a drug as expected.
Centres will apply their expertise in a range of exploratory biomarker discovery tools across scale to identify biomarkers of ‘response’ and disease progression that will ultimately complement and build on the use of NfL.
Research Centres Involved
DNA/RNA analysis
Proteomic studies
Improving outcome measures and reducing trial burden
The systemic immune response
Network changes (magnetoencephalogaphy (MEG) studies)
iPSC model studies
Microbiome Analysis
Creating a BioResource
A bioresource refers to a collection of biological materials or data that can be used for scientific research. EXPERTS-ALS will lead to the development of a deeply phenotyped cohort of biological samples creating a valuable, open access NIHR bioresource. This bioresource will provide a valuable opportunity for the development of stratification and pharmacodynamic biomarkers, as well as to identify the individual biological basis for the candidate therapeutics beyond their effect on blood NfL.