MS Biomarkers in the Clinic: Around the Corner?

Andrew N. Wilner, MD; Charlotte E. Teunissen, PhD

Disclosures

December 20, 2011

Editor's note:

At the 5th Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis in Amsterdam, The Netherlands, Andrew N. Wilner, MD, interviewed Charlotte Teunissen, PhD, Assistant Professor and Head of Neurological Laboratory and Biobank of the Department of Clinical Chemistry at Vrije Universiteit University Medical Center in Amsterdam, on advances in biomarker diagnostics for multiple sclerosis.

Biomarkers in MS: Introduction

Andrew N. Wilner, MD: Here at the ECTRIMS conference, there's a lot of emphasis on biomarkers for multiple sclerosis (MS). Are practicing neurologists using any biomarkers at the moment?

Charlotte Teunissen, PhD: There are oligoclonal bands being used to discriminate MS patients from controls, and they're rather sensitive for MS -- above 90%. They are also very stable.

Dr. Wilner: So they're very sensitive, but not very specific. There are many other neurologic diseases in which oligoclonal bands can occur.

Dr. Teunissen: Yes, that's true. We find that using MRI measures and oligoclonal bands reduces [diagnostic uncertainty]. But this is also a controversial issue currently.

Dr. Wilner: So, what is a biomarker?

Dr. Teunissen: A biomarker is defined as an objective indicator of biological processes in a disease state or a pathological process, or of response to a treatment. For early diagnosis we [already have] very well-established diagnostic criteria. However, for very early diagnosis or risk prediction -- and also for early therapy response prediction -- they could be very valuable.

Dr. Wilner: So right now we have many new treatment options in MS, which we're hearing a lot about at this meeting. But the physician who is face to face with a patient still doesn't have too many clues about which one to choose for a given patient. Could a biomarker be helpful?

Dr. Teunissen: Well, that's one of our aims -- to be able to predict in a relatively short time or beforehand whether our patients will respond to therapy A or therapy B. That would be ideal. I think less ideal, but also very interesting, would be if a response can be predicted after just 1 or 2 months of treatment -- whether there is a relevant biological response or not. Because now doctors evaluate the response to a therapy at a half year or longer.

Dr. Wilner: What kind of physiologic responses could be measured? Is it something in the blood or the spinal fluid?

Dr. Teunissen: Yes. Spinal fluid would be ideal, and that's where most of the current studies are looking. I'm talking mostly about proteomics discovery here.

Dr. Wilner: Researchers have been throwing around this word "proteomics" all week at this conference. Can you tell us what it means exactly?

Dr. Teunissen: For our purposes, all proteins within the cerebrospinal fluid [CSF] are called the proteomes. And all proteins, or the whole proteome, of the cerebrospinal fluid of MS patients are being compared to controls. And this activity is called proteomics, and there are specific tools being used for proteomics. It can be gel-based, also chromatography-based, and there are other methods as well. But the main feature is that all proteins are being compared. [Editor's note: Broadly speaking, a "proteome" refers to all of the proteins expressed and/or present by/in a genome, organism, or tissue.].

Currently, proteomics methods are sensitive enough to measure about 1000 different proteins in CSF simultaneously. So some may be different between MS and controls. You look at the peak concentration and the identity of these proteins to determine if they might be new biomarkers.

Dr. Wilner: Are there any proteins in the spinal fluid of MS patients that are unique to those patients'?

Dr. Teunissen: I have not seen them yet.

Dr. Wilner: So it's more of a question of the amount?

Dr. Teunissen: Yes. Differences in concentration. Though [biomarkers only present in] patients with MS could be possible.

Dr. Wilner: If you didn't know what you were looking for, would you be able to find it?

Dr. Teunissen: Yes, because the technology allows us to look at all proteins. Mass spectrometry will define the identity of the proteins.

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