Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms.

Aakanksha Dixit,Sheila Donnelly,Akane Tanaka,Judith M Greer

doi:10.3390/ijms18102141

Abstract

The evolutionary response to endemic infections with parasitic worms (helminth) was the development of a distinct regulatory immune profile arising from the need to encapsulate the helminths while simultaneously repairing tissue damage. According to the old friend’s hypothesis, the diminished exposure to these parasites in the developed world has resulted in a dysregulated immune response that contributes to the increased incidence of immune mediated diseases such as Multiple Sclerosis (MS). Indeed, the global distribution of MS shows an inverse correlation to the prevalence of helminth infection. On this basis, the possibility of treating MS with helminth infection has been explored in animal models and phase 1 and 2 human clinical trials. However, the possibility also exists that the individual immune modulatory molecules secreted by helminth parasites may offer a more defined therapeutic strategy.

Highlights

Multiple Sclerosis (MS) is an autoimmune demyelinating disease that can manifest as a wide range of clinical signs and symptoms and present with varying severity
Related to this activity is the production of the anti-oxidant peroxiredoxin (FhPrx), which detoxifies the reactive oxygen generated by cellular metabolism [86,87], and the production of FhHDM-1, a peptide that interacts with heme, a toxic by product of haemoglobin digestion [88]
The studies discussed here represent a significant body of evidence that proteins secreted by snail and (B5) heenlmcyinstht poanravsietegs eoftfaetriaounniaqusedreosromurcaenfotrmthee tdaiscceovrcerayroiaf aen,tiw-inhfliacmhmaartoerysudrbusges.qTuheensptelcyifiicngested by the definitive hostf.inding that a single parasite secreted protein, FhHDM-1, can suppress the pathology associated with EAE, preliminary, suggests that understanding the mode of action of this parasite protein may provide a novel starting point in the development of safe effective drugs for treatment of human MS

Summary

Introduction

Multiple Sclerosis (MS) is an autoimmune demyelinating disease that can manifest as a wide range of clinical signs and symptoms and present with varying severity. Perhaps the most compelling evidence in this regard has been the rapid increase in the incidence rates of MS in the developed world over recent years [6,7,8,9] This rise far exceeds the rate of population evolution and implies either the removal of protective factors or the introduction of susceptibility factors in the environment. Perhaps the most compelling environmental relationship is the worldwide inverse correlation between infections with parasitic worms (helminths) and the incidence of autoimmune disease [18] Corroborating this hypothesis, longitudinal and migratory studies evaluating the prevalence of MS in the French West Indies over a period of 20 years showed that increased MS incidence in the region was associated with a significant reduction of parasite infections during the same time period [19]. The fact that administration of anti-helminth drugs resulted in increased MS activity [21], suggests that helminths directly suppress autoimmune diseases and may be the protective environmental factor against the development of MS

Should We Reunite with Our Old Friends the Helminth Parasites?

Testing the Effectiveness of Helminth Infection in Animal Models of MS

Testing the Effectiveness of Helminth Infection in Human Trials

Results

Translating to the Clinic

Conclusions