Journal
ACTA NEUROLOGICA SCANDINAVICA
Volume 146, Issue 4, Pages 375-388Publisher
WILEY
DOI: 10.1111/ane.13698
Keywords
amyotrophic lateral sclerosis; blood matrix effect; clinical trials; neurofilaments; pharmacodynamic biomarkers; prognosis
Categories
Funding
- Barts and the London Charities
- National Institutes of Health
- MND Association UK
- Wellcome Trust UK
- NIHR UK
- Barts Charity UK
- MRC
- ALS Association
Ask authors/readers for more resources
ALS is the most common motor neuron disease among adults, and early diagnosis is crucial. The lack of disease-specific biomarkers in ALS patients poses challenges for clinical trials.
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease among adults. With diagnosis reached relatively late into the disease process, extensive motor cell loss narrows the window for therapeutic opportunities. Clinical heterogeneity in ALS and the lack of disease-specific biomarkers have so far led to large-sized clinical trials with long follow-up needed to define clinical outcomes. In advanced ALS patients, there is presently limited scope to use imaging or invasive cerebrospinal fluid (CSF) collection as a source of disease biomarkers. The development of more patient-friendly and accessible blood biomarker assays is hampered by analytical hurdles like the matrix effect of blood components. However, blood also provides the opportunity to identify disease-specific adaptive changes of the stoichiometry and conformation of target proteins and the endogenous immunological response to low-abundance brain peptides, such as neurofilaments (Nf). Among those biomarkers under investigation in ALS, the change in concentration before or after diagnosis of Nf has been shown to aid prognostication and to allow the a priori stratification of ALS patients into smaller sized and clinically more homogeneous cohorts, supporting more affordable clinical trials. Here, we discuss the technical hurdles affecting reproducible and sensitive biomarker measurement in blood. We also summarize the state of the art of non-CSF biomarkers in the study of prognosis, disease progression, and treatment response. We will then address the potential as disease-specific biomarkers of the newly discovered cryptic peptides which are formed down-stream of TDP-43 loss of function, the hallmark of ALS pathobiology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available