It has long been recognized that there is an inverse relationship between infection with parasitic worms and the development of allergic and autoimmune diseases: people who live in parts of the world where the worms are present have a much lower chance of developing these types of diseases.  Recently it has been shown that live parasitic worms can be used successfully to treat some of these diseases, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). However, there are many drawbacks to using live worms for treatment. It would be preferable to identify the active components of the worms and then use just those components to treat disease. The current project focuses on one such component produced by the liver fluke Fasciola hepatica. This molecule, known as FhHDM1, is a 68 amino acid alpha helical cathelicidin-like peptide. FhHDM1 was tested for its ability to modulate the development and progression of relapsing-remitting EAE when used prior to the onset of disease (prophylactic treatment) or after the first attack of clinical signs of disease (therapeutic treatment). Both prophylactic and therapeutic treatments were protective.  The effects were long-lasting, with mice continuing to show benefits for up to 70 days after treatment. FhHDM1 had no effects on the magnitude or nature of T cell responses, with no skewing of cytokine responses. Instead, FhHDM1 appeared to interact preferentially with monocytes/macrophages, and to block activation of and to inhibit the entry of these cells into the brain parenchyma. Ongoing work is investigating the mechanism by which these cells are prevented from entering the brain. The data show that FhHDM1 provides lasting protection against development of EAE, and suggest that this peptide may be preferable to live parasitic worms as a novel treatment for patients with MS.