Research ArticleMultiple Sclerosis

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease

See allHide authors and affiliations

Science Translational Medicine  26 Oct 2016:
Vol. 8, Issue 362, pp. 362ra146
DOI: 10.1126/scitranslmed.aaf8732

You are currently viewing the abstract.

View Full Text

A repurposed drug for neuroinflammatory disease

Treatment of inflammation-associated progressive neurodegenerative disorders, such as relapsing remitting multiple sclerosis, is challenging. In a new study, Mykicki et al. demonstrate that the drug NDP-MSH, currently approved for treating porphyria, showed potent anti-inflammatory and neuroprotective effects in two mouse models of neuroinflammatory disease. The drug, acting via the melanocortin-1 and orphan nuclear 4 receptors, prevented neuronal cell death by inducing regulatory T cells and preventing the infiltration of pathogenic T cells into the central nervous system.

Abstract

In inflammation-associated progressive neuroinflammatory disorders, such as multiple sclerosis (MS), inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells cause demyelination and neuronal degeneration. Regulatory T cells (Treg) control the activation and infiltration of autoreactive T cells into the central nervous system (CNS). In MS and experimental autoimmune encephalomyelitis (EAE) in mice, Treg function is impaired. We show that a recently approved drug, Nle4-d-Phe7–α-melanocyte–stimulating hormone (NDP-MSH), induced functional Treg, resulting in amelioration of EAE progression in mice. NDP-MSH also prevented immune cell infiltration into the CNS by restoring the integrity of the blood-brain barrier. NDP-MSH exerted long-lasting neuroprotective effects in mice with EAE and prevented excitotoxic death and reestablished action potential firing in mouse and human neurons in vitro. Neuroprotection by NDP-MSH was mediated via signaling through the melanocortin-1 and orphan nuclear 4 receptors in mouse and human neurons. NDP-MSH may be of benefit in treating neuroinflammatory diseases such as relapsing-remitting MS and related disorders.

View Full Text