By Roxanne Lee
Recent discoveries have highlighted the use of the parasite hookworm in treating autoimmune disorders, though the true subject of the research is not the parasite, but the molecules it produces.
It is understandable that using hookworms as treatment in medicine is strange. Hookworms are parasitic nematode worms that infest the small intestines of birds and mammals. Two species in particular infest humans: Anclyostoma duodenale and Necator americanus.
Hookworms attach to the wall of the intestine to drink their hosts’ blood. If it is a light infestation, as most people who have the infection, there will not be any external symptoms. However, a heavy infestation can cause nausea, anemia, cramping, weight loss, abdominal pain, and protein loss.
There are 760 million hookworm infections worldwide and 25 million in the United States, though it used to be more widespread than that.
Their use in medicine comes in part from the hygiene hypothesis, which posits that the lack of exposure to germs and parasites in childhood leaves humans prone to develop more allergies and autoimmune disorders as they mature.
Scientists working at James Cook University in Australia studied the possible link between the decline in parasites due to improved public health and the rise of autoimmune disorders. They, as well as other teams of scientists, have used the parasite in studies of the treatment of autoimmune disorders such as inflammatory bowel disorder and Crohn’s disease, and have repeatedly found that the worms alleviate some of the symptoms. This suggests that diseases became more common as people became less infected with hookworms.
There is an understandable lack of appeal to the idea of purposefully being infested with intestinal parasites, so researchers at James Cook University found a solution that gets the best of the parasites without infecting anyone.
Immunologist Dr. Severine Navarro, co-author of the study, and her colleagues looked for a specific molecule responsible for the effects caused by parasites. To find it, they crushed and made “soup” from them. Of the 100 proteins found in the soup, one of most abundant was anti-inflammatory protein-2, AIP-2, that Hookworms secreted while attached in the gut that bolstered the immune systems of their hosts.
Researchers synthesized AIP-2 separately from the parasite and injected it into mice with asthma, then put mice through range of tests. They found that in the mice with asthma, AIP-2 suppressed airway inflammation. The AIP-2 shifted the balance of immune cells and shifted immune reaction in lung, and stopped high proliferation of T cells in the blood. The protein also changed immune cells in human skin when tested on skin samples of people with dust mite allergy. AIP-2 lessened production of dendritic cells and T cells, signs of a reduced allergy response.
Their eventual goal is to create synthetic versions of a drug to artificially replicate the effects of hookworm on autoimmune disorders. By doing this they would not have to purposefully infect people with the hookworm to get the benefits.
Researchers are in the process of isolating and testing more proteins from the soup, in the hopes of finding more that specifically affect autoimmune disorders,and Navarro and colleagues are now looking for a company to support a clinical trial.