Date Published: 21 July 2006

Can hookworms help against autoimmune diseases ?

Although they are barely 1cm long and can live inside the human gut for up to five years without causing any symptoms, the hookworm may be a lot more than an inconspicuous parasite, it might also hold the key to autoimmune diseases like Crohn's Disease, according to experts based at Nottingham University in England.

In the first clinical trial of its kind in the world, scientists are seeking to establish whether the hookworm, Necator Americanus, could help to reduce symptoms of Crohn's disease and help withthe search for an effective long-term therapy.

Patients are being recruited to test the theory by being deliberately infected with hookworms for a 12-week period. The people who take part in the study might be infected with 10 larvae, administered by medical staff through the skin of the arm. Their progress will be monitored over 12 weeks to see if there is a reduction in Crohn's symptoms. At the end of the study, those people who were infected with hookworms take a short course of tablets that kill the hookworms and flush them from the body.

The Nottingham team believes that hookworms might help to 'down-regulate' the human immune system, to stop it reacting in a way that causes the symptoms of diseases like Crohn's. Autoimmune diseases are caused by an over-active immune response, which causes the body to attack its own tissues. It is thought that the parasites have evolved a way of surviving in the gut by 'turning down' the immune response so the body doesn't attack them.

The study is being conducted by Dr Paul Fortun and Professor Chris Hawkey of the University's Wolfson Digestive Diseases Centre, and Professor David Pritchard, an immunoparasitologist in the School of Pharmacy.

Dr Fortun said:

" If you look at a map of the world, the areas where hookworm is prevalent ? such as sub-Saharan Africa and south-east Asia ? tend to be where inflammatory bowel diseases (IBD) such as Crohn's and ulcerative colitis are extremely rare.

_ Conversely, in developed countries with low levels of hookworm infestation, IBD is prevalent. African-Americans living in the USA have the same rate of IBD as Caucasian Americans, which suggests it is related to environment rather than genes."

He added:

" In order for the parasite to survive, it induces a 'state of tolerance' in the host. It has found a way to counteract the immune system. There is a lot of evidence that inducing this state of tolerance would reverse the problem that causes Crohn's disease."

Hookworms cannot be passed from person to person through normal day-to-day contact. Natural transmission only occurs when hookworm larvae enter the body through the skin when people walk barefoot on contaminated soil. For this reason, hookworm infestation is virtually unknown in the developed world due to modern standards of hygiene and sanitation.

In the study, just 10 larvae are placed on the skin and covered with a plaster, so they are not dislodged. Over a period of hours, the larvae enter the skin and then gradually make their way to the intestine, via the lung. According to Professor Pritchard, who has deliberately infected himself in the past, provided that the dosage is carefully regulated the only sensation is a mild itching when the larvae are on the skin. The tiny number of hookworms means that ill effects are unlikely.

The format is a 'double-blind, placebo-controlled' study, which means half the patient volunteers will be given the larvae, and half will get a placebo in the form of histamine that replicates the itching sensation on the surface of the skin. The study follows on from work by Professor Pritchard and Professor John Britton, which is exploring the use of hookworms in the treatment of hayfever and asthma.

Crohn's Disease is a chronic ongoing condition that most commonly affects the small intestine and colon. It causes inflammation, deep ulcers and scarring to the wall of the intestine, with main symptoms including pain in the abdomen, diarrhoea, fatigue and weight loss. It affects up to 60,000 people in the UK, with 3?6,000 new cases being diagnosed each year. At the present time there is no medical cure for Crohn's Disease. Normal treatment includes steroids, which cannot be taken long-term, and immune suppressant drugs.

However, if the new study is successful, drug therapies developed in the future might mimic the effect of the hookworm and may even be able to stop the condition occurring at all, scientists hope.

The study is being funded with a grant from the Broad Foundation, based in Los Angeles. Volunteer patients will be recruited to centres in Nottingham, Mansfield, Derby and Rotherham.

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