Study Identifies Three Distinct Subtypes of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic illness that affects an individual’s central nervous system. The disease manifests differently in each individual and has varying trajectories, which makes it difficult to manage. It also has no cure. New research has identified three subtypes of the disease based on immune markers observed in participants’ blood.

For the research, a team of investigators led by Professor Heinz Wiendl, a professor at the University of Münster, conducted a comprehensive analysis of the immunological properties of different blood samples collected from more than 300 early multiple sclerosis patients and a validation group made up of 232 patients with the same illness. In both groups, the researchers determined that cellular immune signatures split into three separate subtypes: E1, E2 and E3.

The investigators explored the characteristics of the different subtypes, observing that E1 had modifications in the CD4 T-cells, with earlier structural brain damage, growth in inflammatory cytokines, higher disability and more severe illness. The E2 subtype had modifications in natural killer cells while E3 was characterized by modifications in the CD8 T cells.

The investigators also observed that the subtypes were linked to distinct clinical illness trajectories, noting that patients with the E1 endophenotype had higher degrees of illness severity and early structural brain damage.

At baseline, patients with the E3 endophenotype also had more gadolinium-enhancing lesions, with the investigators noting that this subtype was also linked to increase in cell numbers in intrathecal immunoglobulin G synthesis and cerebrospinal fluid. In addition, patients with the E3 subtype presented with higher inflammatory illness activity.

In their report, the investigators termed the E1 endophenotype as degenerative and the E3 endophenotype as inflammatory, noting that each sample has a slightly different response to therapy and illness trajectory. The research team hopes that with further validation, learning the immune signature of a patient’s blood prior to commencing immunomodulatory therapy may help forecast illness trajectory and help formulate more personalized treatments.

In an interview, Wiendl explained that characterizing a patient’s immune signature at diagnosis would help determine likely illness trajectory while also allowing clinicians to refine the selected immune therapy. Wiendl, who chairs the institution’s neurology department, added that this was a rationale to underpin the precision medicine of the future.

The research’s findings were reported last month in “Science Translational Medicine.” Support for the study was provided by grants from the Hermann and Lilly Schilling Foundation, the German Research Council and the Federal Ministry of Education and Research.

It is noteworthy that many other entities, such as Clene Inc. (NASDAQ: CLNN), are focusing on developing next-generation treatments for MS. It is just a matter of time before patients have access to affordable treatment options that will offer them better clinical outcomes compared to the current medications.

NOTE TO INVESTORS: The latest news and updates relating to Clene Inc. (NASDAQ: CLNN) are available in the company’s newsroom at

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