Biomarkers and diagnostic tests pipeline

A forum to discuss research on the origins of MS and its development.

Biomarkers and diagnostic tests pipeline

Postby frodo » Tue Jun 05, 2018 4:31 am

Diagnosis in MS is based in clinical finding. Usually all tests require to prove that there are lesions in the brain "disseminated" in time and space. This means that MS cannot be diagnosed until damage is big enough to be seen.

In fact, if the damage done by MS is not big enough it is not even called MS. People with demyelinating lesions similar to MS are called RIS and are considered "non-MS" patients, even if they share the same MS-underlying condition.

Therefore research into biomarkers that could show that underlying condition are important for early diagnosis. But even if a lot of them are known, they have a protocol for approval similar to those for drugs. Following https://www.nature.com/articles/nrneurol.2015.173 is like:



There is a freely available review at [https://www.researchgate.net/publication/312361609_Biomarkers_of_multiple_sclerosis_current_findings] about the status of knowledge as of 2017, and a wide classification in groups in [https://academic.oup.com/brain/article/127/7/1463/266245]

I am gonna try to maintain here a review about some diagnostic tests that are still not in clinical use. Most of them also will serve in the future to monitor the evolution and response to medications:

Advanced MRI technologies

*DTI: MRI that shows Normal Appearing White Matter
*SWI: Susceptibility weighted Imaging: Shows veins, including the central vein of MS lesions.
*MRN: magnetic resonance neurography: Shows damage in peripheral nervous system.

Other imaging technologies

*PET: Positron emission tomography: Can show activated microglia. They are based in a kind of contrast called radioligand. The most recently found is [18F]GE-180 (https://ejnmmires.springeropen.com/arti ... 017-0340-x)
*OCT: Optical coherence tomography: Inspection of the eye's retina.

Body Fluid biomarkers

*CSF oligoclonal bands: Currently used in clinical diagnosis
*CSF specific proteins
*MRZ Reaction: Measles Rubeola and Zoster reaction (two positives out of three)
*Light chains (pieces of immunoglobulins) in blood or CSF
*Neurofilament light: [2]
*microRNAs (miRNAs) in blood or CSF: [1][2]. They are associated with "circulated exosomes" (Exosomes are nano-sized particles shed by almost all cell types in the body and are packed with micro-RNAs and other types of small RNA)
*Cytokines and interleukins (ILs): Serum level of interleukin 36 in patients with multiple sclerosis (https://www.tandfonline.com/doi/abs/10. ... ode=ljii20)
*RNA analysis: Test to test several properties of RNA in blood based in this paper: https://www.ncbi.nlm.nih.gov/pubmed/23748426. Explained here [http://patientactivationnetwork.com/wp-content/uploads/2017/08/IQuity_ResearchOverview_MS.pdf]. It is commercially available here: https://www.iquitylabs.com/lab-login/
*Neurofilaments ELISA/NFL tests. Are also commercially available. For example https://www.ibl-international.com/en/ne ... ight-elisa

In the news:

*micro-RNAs: Nine unique micro-RNA molecules that differentiate between two MS sub-types: relapsing-remitting MS (RRMS) and progressive MS [https://www.sciencedaily.com/releases/2017/10/171030095425.htm]
*Osteopontin in blood [https://www.ncbi.nlm.nih.gov/pubmed/29346446]
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frodo
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