Heterogeneity of MS Makes New Disease Biomarker Discovery Difficult

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The treatment landscape for multiple sclerosis continues to get more complex month to month, which makes biomarker discovery increasingly important for treating the disease, said Suhayl Dhib-Jalbut, MD, professor at the Rutgers University Robert Wood Johnson Medical School, during his session at the 2014 Joint ACTRIMS-ECTRIMS Meeting in Boston, Massachusetts.

The treatment landscape for multiple sclerosis (MS) continues to get more complex month to month, which makes biomarker discovery increasingly important for treating the disease, according to Suhayl Dhib-Jalbut, MD, professor at the Rutgers University Robert Wood Johnson Medical School.

There are many significant reasons why biomarker discovery in MS is crucial, including early diagnosis, assessing disease activity, and predicting treatment response and treatment complications, Dhib-Jalbut said during his talk “Biomarkers of Treatment Response to MS Disease Therapies,” at the 2014 Joint ACTRIMS-ECTRIMS Meeting in Boston, Massachusetts from September 10-13.

For instance, alemtuzumab — which is not available in the United States, but is available elsewhere in the world — is associated with autoimmune complications in patients.

The biomarkers that are known to be clinically useful for monitoring MS therapy include:

Biomarker

Condition

JC virus assay

Progressive multifocal leukoencephalopathy risk with natalizumab

Neutralizing antibodies

Interferon unresponsiveness

HLA DR & DQ alleles, transforming growth factor beta/interleukin (IL)-18

Glatiramer response

IL-10/IL-17/interferon-beta

Interferon response

IL-21

Alemtuzumab autoimmunity

CD 56^Bright

Daclizumab therapy

MRI

Interferon response

However, disease heterogeneity is a challenge to biomarker discovery, according to Dhib-Jalbut. For instance, the disease is pathologically heterogeneous, there are inconsistent immune findings, and variable clinical courses.

Furthermore, the fact that response to disease-modifying drugs varies from patient to patient is not only important to keep in mind when choosing which therapy to use, but it makes finding new biomarkers difficult, he said.

During his talk, Dhib-Jalbut highlighted potentially useful biomarkers such as the VLA-4 integrin, CD34 cells, and cerebral spinal fluid, for natalizumab. Also, the CD4:CD8 ratio and decreased T-cells or B-cells could be useful with fingolimod.