MS: Research in Brief

Biomarkers in the blood might serve as effective tools in the diagnosis and therapeutic targeting of MS patients. A short washout period of natalizumab of 8 to 12 weeks leads to less MS activity before initiating fingolimod. Researchers have identified a pivotal gene in MS that regulates human leukocyte antigen class II, the strongest genetic factor in MS.

Study 1: Lack of Biomarkers to Distinguish Forms of MS 

• Current challenges associated with management of MS patients stem from the lack of biomarkers to stratify different clinical forms of the disease.

• Development of minimally invasive biomarkers would help discriminate among the different forms of the disease and predict treatment response.

• These researchers analyzed a set of 30 different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive, and primary progressive MS) and 53 healthy controls.

• Divergent clinical and histology-based MS forms were associated with distinct profiles of circulating plasma protein biomarkers (HGF, Eotaxin/CCL11, EGF, and MIP-1β/CCL4).

• Distinct signatures were composed of chemokines and growth/angiogenic factors.

• Vascular endothelial growth factor was overexpressed in secondary progressive MS.

• These factors might reveal new insights into the complex mechanisms underlying MS pathophysiology.

Study 2: Optimal Timing of Fingolimod Following Natalizumab Discontinuation

• There is no evidence-based guidance on the optimal timing for initiating fingolimod therapy following natalizumab discontinuation in MS to avoid potentially harmful additive effects on immune surveillance and still maintain appropriate disease control.

• These researchers conducted a double-blind, randomized, parallel-group study of 142 patients with relapsing-remitting MS.

• The patients were randomized to 8-, 12-, or 16-week washout periods followed by fingolimod treatment over 32 weeks from the last natalizumab infusion.

• Generally, a shorter washout period was associated with less MS disease activity.

• Washout periods of 8 weeks or 12 weeks were associated with less MRI and clinical disease activity compared with the 16-week washout.

• For optimal disease control, fingolimod treatment should be initiated between 8 and 12 weeks after discontinuation of natalizumab infusions.

Study 3: Genetic Factor’s Links to MS

• The strongest genetic factor in MS is the human leukocyte antigen class II.

• The C-type lectin CLEC16A gene is known to be associated with several autoimmune diseases, including MS.

• These researchers found a strong upregulation of CLEC16A expression in the white matter of 14 MS patients as compared to 11 non-demented controls.

• CLEC16A levels were also significantly enhanced in peripheral blood mononuclear cells of 69 MS patients versus 46 healthy controls.

• Treatment of antigen-presenting cells with vitamin D, a key protective environmental factor in MS, down-modulated CLEC16A in parallel with human leukocyte antigen class II.

• The researchers identified CLEC16A as a pivotal gene in MS that serves as a direct regulator of the human leukocyte antigen class II pathway in antigen-presenting cells.

Take-home Messages:

• Evaluation of circulating biomarkers might become an effective tool in MS diagnosis and in more personalized therapy.

• Before initiating fingolimod therapy, shorter natalizumab washout periods are associated with less MRI disease activity than longer washout periods.

• Researchers have taken the first step in coupling MS-associated genes to the regulation of human leukocyte antigen class II, the strongest genetic factor in MS.