For millions of years, parasitic worms have had to survive inside animals without being destroyed by their hosts' immune systems. To do that, they have evolved remarkably effective ways of dampening the immune response.
Authors
- Eilis Dowd
Professor of Pharmacology and Therapeutics, University of Galway
- Sienna Stucke
PhD Candidate in Pharmacology and Therapeutics, University of Galway
Scientists are now trying to understand those tricks and work out whether they could be turned into medicines for diseases resulting from overactive immune systems.
Parasitic worms, also known as helminths, include roundworms, tapeworms, hookworms and flukes. Many live and feed in the intestines of their hosts, including humans. They still infect up to 1.5 billion people worldwide each year.
Although they can be unpleasant, these parasites deserve some grudging respect. They have evolved ways to survive inside their hosts for years and even decades. For scientists interested in autoimmune, inflammatory and allergic conditions, that's a remarkable skill.
The human immune system walks a constant tightrope - it must be aggressive enough to fight off viruses, bacteria and parasites, but controlled enough to avoid damaging the body's own tissues. Sometimes that balance breaks down.
There are three main ways the immune system can turn against its host. In autoimmune diseases, the immune system mistakenly attacks the body's own cells and tissues. In inflammatory conditions, an excessive or prolonged immune response can damage healthy tissue and cause chronic symptoms. In allergic diseases, the immune system overreacts to otherwise harmless substances, treating them as dangerous threats.
Over time, scientists noticed that rates of these immune conditions were much higher in countries that had largely rid themselves of parasite infections. This led to the old friends hypothesis , which suggested that our co-evolution with the parasites inside us may have benefited our immune systems.
Scientists then wondered whether deliberately infecting patients with live parasites or their eggs could be used as a therapy. By the early 2000s, the idea had moved from an intriguing hypothesis into human clinical trials. One early example involved Trichuris suis, the pig whipworm. Patients with inflammatory bowel diseases were given 2,500 whipworm eggs to swallow, and over time, their disease symptoms improved.
However, deliberately infecting patients with parasites is a difficult idea to get people to accept. For this reason, researchers began to take a closer look at our "old friends" and what tricks they evolved to deceive our immune systems. It turns out that they secrete a whole array of molecules that can convince the immune system to allow them to live and feed inside their hosts. These molecules act on the immune cells to tamp down their activity.
Now, instead of giving patients live parasites, there is the intriguing possibility of using their molecules as drugs to alter or regulate the immune system.
Hundreds of studies have now investigated worm-derived molecules from dozens of parasite species. In research published in Scientific Reports and Molecular Therapy , we gathered this evidence together and showed that parasitic molecules calm the immune system in animal models of asthma, arthritis, rhinitis, colitis, sepsis and diabetes.
Animals with asthma could breathe more easily, those with arthritis had less pain and more mobility, those with sepsis did not die of septic shock, and so on across all the disease models investigated.
In another piece of research, from the University of Galway in Ireland, scientists prevented multiple sclerosis in mice treated with a molecule from the liver fluke .
Multiple sclerosis shares something important with the other conditions mentioned above - it is an autoimmune disease in which the immune system mistakenly attacks nerve cells, impairing their function. But multiple sclerosis is also unique because it is the only brain disease in which molecules from parasites have been tested as potential treatments.
Could parasite molecules have beneficial effects for other brain conditions where inflammation plays a role? Inflammation is involved in many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, and coincidentally, incidences of these conditions have also risen since we largely banished parasites.
Are we there yet?
There is still a long road between an intriguing molecule and a medicine. A drug that works in a mouse or rat can fail in humans because our biology is more complex. But there are reasons for cautious optimism. Scientists can now isolate the molecules parasites produce, identify the processes they affect in the human body and modify them into potential drugs. AI could accelerate that search by helping scientists sift through vast numbers of molecules and predict which are most likely to work.
The hope is not that parasites themselves will become medicines, but that millions of years of evolution may have already solved some of the biological problems we are still trying to understand - and that new tools might help us borrow some of their answers.
Some of the most valuable medicines have come from unlikely places. It may be that one of nature's least popular creatures has been carrying important lessons about controlling inflammation all along.
Professor Eilis Dowd receives funding from the Michael J Fox Foundation for Parkinson's Research, the European Union's Marie Skłodowksa-Curie Actions, Taighde Éireann - Research Ireland, the Galway University Foundation and the University of Galway.
Sienna Stucke receives funding from Galway University Foundation.
