Inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination

Brain, 2011 · DOI: 10.1093/brain/awr199 · Published: September 1, 2011

Simple Explanation

Tumor necrosis factor (TNF) is a molecule that can exist in two forms, soluble and transmembrane. This study found that selectively blocking the soluble form of TNF improved outcomes in a mouse model of multiple sclerosis. The researchers used a drug called XPro1595 to block soluble TNF and compared its effects to a drug called etanercept, which blocks both soluble and transmembrane TNF. They found that only XPro1595 improved the condition of the mice. The improvement seen with XPro1595 was linked to the preservation of nerve fibers and improved myelin, the protective coating around nerves. This suggests that targeting soluble TNF could be a new way to treat multiple sclerosis.

Study Duration

Not specified

Participants

Female C57BL/6 mice 2- to 4-months-old

Evidence Level

Not specified

Key Findings

1
Selective inhibition of soluble TNF with XPro1595 improves the clinical outcome in experimental autoimmune encephalomyelitis (EAE).
2
XPro1595 treatment is associated with axon preservation and improved myelin compaction.
3
XPro1595 promotes remyelination and increases the number of oligodendrocyte precursors.

Research Summary

This study investigates the distinct roles of soluble TNF and transmembrane TNF in experimental autoimmune encephalomyelitis (EAE) using pharmacological inhibitors. The researchers found that selective inhibition of soluble TNF with XPro1595 improves functional recovery, axon preservation, and remyelination in a murine model of multiple sclerosis. The study also provides a complete investigation of TNF receptor cellular localization in the spinal cord of EAE mice and patients affected by progressive multiple sclerosis, providing a basis for a better understanding of the role of TNF signalling.

Practical Implications

Therapeutic Target

Selective inhibition of soluble TNF may be an effective therapeutic strategy for multiple sclerosis.

Neuroprotection and Remyelination

Preserving transmembrane TNF signalling is crucial for neuroprotection and remyelination in multiple sclerosis.

Clinical Trials

XPro1595 represents a promising new candidate to be added to the limited repertoire of multiple sclerosis modulating drugs, ﬁnally opening the door to the introduction of a TNF inhibitor into multiple sclerosis therapy.

Study Limitations

1
The study is performed on a mouse model, and results may not directly translate to human multiple sclerosis.
2
The mechanisms underlying the neuroprotective effects of transmembrane TNF are not fully elucidated.
3
The study does not fully investigate the role of lymphotoxin.

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