Parasitic worms could offer new treatment hope for MS patients

University of NottinghamMar 1 2012

Parasitic worms could offer a new treatment hope for patients suffering from the autoimmune disease multiple sclerosis, scientists believe.

Academics at The University of Nottingham have begun recruiting people suffering from the neurological condition on to a trial that will see them infected with a low, harmless dose of the helminth parasite Necator americanus - or hookworm.

The scientists are hoping to prove that the presence of hookworms in the body switches off the mechanism by which the body's immune system becomes overactive - the main cause of MS - and can reduce both the severity of symptoms and the number of relapses experienced by the patients.

The study is being led by Cris Constantinescu, Professor of Neurology in the University's School of Clinical Sciences and a leading MS expert, and David Pritchard, Professor of Parasite Immunology in the University's School of Pharmacy, who has spent decades studying the biology of the hookworm.

Professor Pritchard said: "This study appears counter-intuitive - we are introducing a parasite which is by definition harmful, to act as a stimulus to moderate disease. As a safeguard the hookworms are being used in carefully controlled and monitored conditions, and if successful could herald a much-needed therapy for MS patients.

"Currently, there are many MS patients for whom conventional medicines are ineffective or are associated with unwanted side effects. Hookworms have an innate ability to moderate the immune system to allow them to survive in the body for years. This moderation may have a bystander effect on the progression of MS."

The study team is in the process of recruiting more than 70 patients from the Nottingham and Derby areas who suffer from the most common type of the disease, relapsing remitting MS (RRMS), in which patients symptoms such as vision problems, dizziness and fatigue, appear and then fade away either partially or completely, and secondary progressive MS with superimposed relapses.

Half of the patients on the trial, funded with -400,000 from the MS Society, will receive a low dose of the hookworms -25 of the microscopic larvae - on a plaster applied to the arm, while the other half will receive a placebo plaster.

Once the larvae come into contact with the skin they work their way through into the blood stream until they reach the lungs where they are coughed up and swallowed to get to their final destination, the gut, where they survive by latching on to the gut lining and feeding on the host's blood. The worms do not multiply in the host but reproduce by producing fertile eggs, which are expelled in faecal matter. These hatch into infective larvae outside the body, and are used to infect patients.

The patients on the study will be given regular blood tests to check they are not anaemic - a sign that the dose of hookworms could be too high for that individual. Prior safety studies indicate that this is unlikely to happen, and de-worming will take place if it does.

At the beginning of the trial, the participants will undergo a MRI scan to record the scarring or lesions on the brain which are present in MS patients. Over the course of nine months, all the patients will be scanned on a regular basis for new or worsening lesions which can be a tell-tale sign of relapse.

At the end of the trial, the results of the two patient groups will be compared to establish whether the hookworms have been successful in damping down the immune system of the patients, keeping their symptoms in check and preventing relapses.

Professor Pritchard has been studying hookworms for almost two decades since his work as a zoologist took him to remote villages in Papua New Guinea to investigate the parasites in the indigenous population.

Evidence showing that natural parasitic infection led to a lower incidence of other immune-related diseases such as allergy prompted research into the therapeutic potential of worm infection.

Before they were able to put the worms into clinical trial to test their efficacy against human disease, the team needed to establish they were safe to use and had no ill effect while passing through the lungs.

Initially, the researchers volunteered to be infected themselves to establish a safe dosage at which there were no side effects, before participants suffering from asthma and rhinitis were recruited to clinical trials in which they were infected for a period of 12 weeks and studied to ensure there was no effect on respiratory function as parasites migrated through the lungs.

Following the successful outcome of the safety trials, the team has undergone the necessary process of having the hookworms approved as an investigational medicinal product by the Medicines and Healthcare Products Regulatory Agency (MHRA).