Worms to the Rescue: Immunomodulators from Parasitic Worms for Autoimmune Diseases — ASN Events
  1. Schedule
  2. Session 12: Poster Session D - Including Happy Hour & Trade Display
  3. Worms to the Rescue: Immunomodulators from Parasitic Worms for Autoimmune Diseases

Worms to the Rescue: Immunomodulators from Parasitic Worms for Autoimmune Diseases (#436)

Sandeep Chhabra 1 , Shih Chieh Chang 1 , Hai M. Nguyen 2 , Redwan Huq 3 , Mark R. Tanner 3 , Luz M. Londono 4 , Sanjeev K. Upadhyay 2 , Mariel Gindin 5 , Peter J. Hotez 6 , Jesus G. Valenzuela 7 , Biswaranjan Mohanty 1 , James D Swarbrick 1 , Heike Wulff 2 , Shawn P. Iadonato , George A. Gutman , Christine Beeton 3 , Michael W. Pennington 8 , George K. Chandy 2 , Raymond S. Norton 1
  1. MIPS (Monash institute of Pharmaceutical Sciences), Parkville, VIC, Australia
  2. Departments of Physiology and Biophysics, Pharmacology, and Microbiology and Molecular Genetics, School of Medicine, University of California, , Irvine, CA 92697, USA
  3. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
  4. Kineta, Inc., , Seattle, , WA 98109
  5. Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University , Washington DC 20052
  6. Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas 77030
  7. Vector Molecular Biology Section, LMVR, NIAID, NIH , Rockville, MD, 20852
  8. Peptides International , 11621 Electron Drive, Louisville , KY 40299, USA

Autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes (T1D), rheumatoid arthritis (RA), ulcerative colitis and Crohn’s disease are characterized by an immune-mediated attack on the body’s own tissues. These disorders are found to be more frequent in the affluent population of developed countries, possibly owing to improved hygiene, vaccination, and the use of antibiotics. The ‘hygiene hypothesis’ states that limited exposure to bacterial and viral infections during early childhood results in an insufficient stimulation of regulatory T cells (Treg), which in turn results in inappropriate development of the immune system. These cells dampen the immune response and curb autoimmunity by stimulating release of cytokines, which in turn prevent the production of effector T cells (Teff) responsible for triggering autoimmune reactions.


Autoimmune disease patients treated with parasitic worm infections showed improved disease symptoms and had no adverse effects 1, 2. However, infants and elderly patients have an underdeveloped or compromised immune system and treatment with parasite infections may increase their susceptibility to other bacterial and viral infections. Our aim is to identify substances secreted by the parasites into the host system and test for their ability to modulate the immune system.


In the current study, we have identified and characterized two types of worm peptides, one that is secreted into the host and the other as the C-terminal domain of a larger protein. The solution structures of both peptides were solved using conventional NMR experiments. The electrophysiological data confirms that both peptides are blockers of human potassium ion channel (Kv1.3). The peptides demonstrated immunomodulatory activities by suppressing rat effector memory T cell proliferation, pro-inflammatory cytokines production by human T cells, and delayed-type hypersensitivity in rats. Our results provide a mechanistic basis for pro-biotic worm therapy and suggest that these or related peptides and proteins could supplant the need for worm therapy.

  1. Fleming JO, et al. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Mult Scler 17, 743-754 (2011).
  2. Weinstock JV. Autoimmunity: The worm returns. Nature 491, 183-185 (2012).