̽��ֱ�� of Cambridge - allergy

Study of peanut allergy therapy shows 84 per cent success

fpjl2 — Thu, 30 Jan 2014 10:47:30 +0000

Allergy experts have found that 84 and 91 per cent of the two groups of children treated with a new form of immunotherapy could eat at least five peanuts a day.

̽��ֱ��phase 2 trial - the largest of its kind worldwide - used oral immunotherapy (OIT), in which peanut protein is consumed in increasingly larger amounts on a regular basis to build up tolerance. ̽��ֱ��results are published today in ̽��ֱ��Lancet.

̽��ֱ��research involved young people, aged between seven and sixteen, eating daily doses of peanut protein - starting with a tiny dose and slowly building up over four to six months.

After 6 months of OIT, 84–91% of the children could safely tolerate daily ingestion of 800 mg of peanut protein (roughly the equivalent of five peanuts), at least 25 times as much peanut protein as they could before the therapy.

Peanut allergy affects around half a million people in the UK and over 10 million people across the globe. It’s the most common cause of fatal food allergy reactions and, unlike other childhood food allergies such as cow’s milk, peanut allergy rarely goes away. People with peanut allergy risk anaphylactic shock or even death if they become accidentally exposed to peanut.

̽��ֱ��Cambridge allergy research team, led by Dr Andrew Clark and Dr Pamela Ewan from the ̽��ֱ��’s Department of Medicine, have been leading allergy research for more than 20 years.

“Before treatment children and their parents would check every food label and avoiding eating out in restaurants,” said Clark. “Now most of the patients in the trial can safely eat at least five whole peanuts. ̽��ֱ��families involved in this study say that it has changed their lives dramatically.”

“This large study is the first of its kind in the world to have had such a positive outcome, and is an important advance in peanut allergy research,” added Ewan.
“However, further studies in wider populations are needed. It is important to note that OIT is not a treatment people should try on their own and should only be done by medical professionals in specialist settings.”

In the first part of the trial, 99 children with varying severities of peanut allergy were randomly assigned to receive either 26 weeks of OIT or peanut avoidance (the present standard of care). All the children then participated in a double-blind placebo-controlled oral food challenge during which they gradually consumed increasing amounts of peanut protein under medical supervision to determine at what level they experienced allergic symptoms. In the second part, the control group was offered 26 weeks of OIT followed by a final food challenge.

After 6 months of therapy, 24 of 39 children (62%) who received OIT in the first phase passed the challenge and tolerated a daily dose of 1400 mg of peanut protein, roughly equivalent to 10 peanuts (an amount unlikely to be encountered accidentally), compared with none of those in the control group. After the second phase, 54% tolerated the challenge. Food-allergy specific quality of life scores also improved after OIT.

Although a fifth of those receiving OIT reported adverse events, most were mild with oral itching being the most common.

Lena Barden, 11, from Histon in Cambridgeshire, said: “I felt like I had won a prize after I found out I had been picked for the active group. It meant a trip to the hospital every two weeks. A year later I could eat 5 whole peanuts with no reaction at all. ̽��ֱ��trial has been an experience and adventure that has changed my life and I’ve had so much fun. But I still hate peanuts!”

Thomas Baragwanath, 16, from Holbeach, Lincolnshire, said: “ ̽��ֱ��trial has helped me so much. I don’t have to worry when I go out with my friends about what I’m eating and where it’s come from ‘What’s in it? Where’s it been prepared?’ - I don’t have to worry at all.”

̽��ֱ��trial was carried out over five and a half years in the NIHR Wellcome Trust Clinical Research Facility at Addenbrooke’s, part of Cambridge ̽��ֱ�� Hospitals (CUH). It was funded by the MRC-NIHR partnership through the Efficacy and Mechanism Evaluation (EME) Programme. Initial pilot work was funded by the Evelyn Trust, Cambridge.

̽��ֱ��next step is to make peanut immunotherapy widely available to patients. Further investigation and a licensing review will be required to obtain a product licence from the regulatory authorities, which will take several years. In the meantime, Cambridge ̽��ֱ�� Hospitals is planning to open a peanut allergy clinic that would make a range of services, including immunotherapy on a named patient basis, available to patients.

For further information about the development of peanut immunotherapy and when it will become available in clinics, visit www.cambridgeallergytherapy.com.

For more information on this research, please contact Adrian Ient: adrian.ient@addenbrookes.nhs.uk

Inset image: Dr Clark in the allergy clinic at Addenbrooke's Hospital

A new therapy for peanut allergy has been successful in the majority of the 99 children who took part in a clinical trial.

̽��ֱ��trial has been an experience and adventure that has changed my life and I’ve had so much fun. But I still hate peanuts!

Lena Barden, 11, from Histon in Cambridgeshire

Daniella Segura

Peanuts

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.

Yes

Licence type:

Attribution

Study shows new peanut allergy treatment works

ns480 — Mon, 21 Mar 2011 11:58:25 +0000

̽��ֱ��trial, from the group of Dr Pamela Ewan of the Department of Medicine and conducted at Addenbrooke's Hospital, involved a careful regime of feeding chocolate containing peanut flour in gradually increasing doses to patients with severe peanut allergies.

Following on from a small clinical trial conducted in 2009, the allergy team carried out a larger trial involving 22 children.

Before beginning the treatment, the children involved in the study reacted to tiny amounts of peanut. After treatment, 19 of 22 children were able to eat five peanuts a day; two had partial success - eating two to three peanuts a day; and one dropped out of the study at the start.

Dr Andrew Clark, who led the clinical trial, said: "This is the first time that a peanut allergy study has shown such a high level of success and proves that it is possible for peanut allergic patients to eat peanuts without fear of a severe reaction."

̽��ֱ��children and teenagers attended the hospital's clinical research facility to undergo the desensitisation treatment, which still proved effective six months on.

Peanut allergy is common, affecting between one and two percent of young children, and can cause severe or even fatal reactions. There is currently no satisfactory treatment. ̽��ֱ��diagnosis has a major impact on families, because of the fear of a severe reaction and anxiety in making food choices.

" ̽��ֱ��lives of the families involved in this trial have been transformed," said Dr Clark. " ̽��ֱ��amount of peanut that could be tolerated by the children and teenagers on this trial increased 1000-fold."

Studies of peanut immunotherapy from other centres, using different regimes have been less successful. ̽��ֱ��Cambridge regime involves more gradual increases in dose but eventually a much higher dose of peanut is tolerated.

"This treatment could drastically improve the lives of those currently suffering with severe peanut allergies," said Dr Maher Khaled of Cambridge Enterprise, the ̽��ֱ��'s commercialisation group. "We are currently looking to make this groundbreaking treatment more widely available."

̽��ֱ��findings are published today, 18 March, in the journal Clinical and Experimental Allergy. ̽��ֱ��study was supported by a grant from the Evelyn Trust, and further work is supported by the National Institute for Health Research.

Allergy experts at the ̽��ֱ�� of Cambridge have convincing evidence that a new treatment for peanut allergies is effective, following a three-year trial.

This is the first time that a peanut allergy study has shown such a high level of success and proves that it is possible for peanut allergic patients to eat peanuts without fear of a severe reaction.

Dr Andrew Clark

EuroMagic from Flickr

peanuts

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.

Yes

Parasites: the master manipulators

tdk25 — Sat, 01 Sep 2007 00:00:00 +0000

̽��ֱ��human race used to have a consensus attitude towards the organisms that we call parasites. They were simply pests, causative agents of disease that warranted nothing else other than extermination. As soon as new life-cycles were described in the literature, the race began to find a way of interrupting transmission and end the misery. ̽��ֱ��literature is therefore full of examples of control programmes for just about every parasite that has ever been identified. Some, such as the programme against the guinea worm, Dracunculus medinensis, have been so successful that complete eradication is now on the World Health Organization’s agenda.

As we wave goodbye to the guinea worm, it will be time to re-visit the hit-list, and to see how far we’ve progressed. In doing so, we are likely to observe that not much has changed. In fact, the guinea worm is the only parasitic infection that has ever been described and then systematically eradicated. There are even signs that the parasitic fauna of the planet is flourishing – recent estimates put the toll of malaria at between 300 and 660 million cases a year, and there are still hundreds of millions of people infected by each of several parasitic worm species. This group includes the trematode parasite Schistosoma mansoni – a blood fluke that infects approximately 200 million people in the tropics and sub-tropics, and which has been the focus of research efforts at the ̽��ֱ�� of Cambridge Department of Pathology for the past 30 years.

Fighting the fluke

Theodor Bilharz formally described schistosome parasites in 1851, at which point the centimetre-long, red-blood-cell-eating worm joined the most-wanted list. Like every other parasitic infection, S. mansoni was viewed with fear and loathing – and with good reason. Infection occurs through contact with free-living larvae in freshwater, with rapid penetration of intact human skin. ̽��ֱ��adults live in the mesenteric veins between the liver and gut. Females produce eggs that become trapped in the liver, promoting an inflammatory response that eventually leads to a form of hepatic fibrosis and portal hypertension. About half the eggs pass through the gut wall, each puncture causing a small amount of blood to be lost. As the worm burden increases with repeated exposure, so the number of eggs in both the liver and gut increases, leading to ever more severe disease.

Early attempts at large-scale control of schistosome infections relied on crude drugs and environmental modification, with success in some areas, but in most places the parasite persisted. Although treatment (praziquantel) is available, re-infection occurs rapidly, especially in children. ̽��ֱ��lack of effective, non-toxic medicine, and the success of vaccination programmes against bacterial diseases, led to the emergence of renewed research efforts aimed at understanding the biology of the worm and its relationship with the human host.

But, despite promises of an anti-schistosome vaccine ‘within five years’ for the past 20 years or so, there is still no vaccine available, because we don’t yet understand the biology of the schistosome worm. Like a fractal puzzle, as we peer more closely we see even greater complexity.

Keeping things quiet

Such is the intimate relationship between host and parasite that we can use the study of schistosome parasites to understand how humans work. One of the key questions that has kept scientists busy is how schistosomes manage to evade the immune response for extended periods. It has been estimated that adult worms live for up to 10 years in their human host. To make this possible, the worms have evolved several mechanisms for diverting, blocking and repressing the immune response. ̽��ֱ��adult worms coat themselves in host proteins to appear invisible to the immune system. They induce the host to produce ineffective immune responses and they manipulate host cells to produce molecules that signal a general downregulation of the host’s response. This essentially produces a drowsy immune response with impaired vision against a camouflaged target – perfect conditions for the parasite to thrive and reproduce

Recent studies in Cambridge in the laboratory of Professor David Dunne have demonstrated the magnitude of this repressive effect by treating people who are already infected with the parasite and measuring their immune responses before and after taking praziquantel. Responses that are thought to be effective against the parasite often increase several fold after drug treatment, and this ‘boosting’ of the host’s ability to respond appears to help prevent re-infection in the future. Recently, the scientists also reported that the ability to respond after treatment is genetically restricted – an observation that has important implications for the development of any therapy or vaccine that relies on increasing the magnitude of the immune response for its protective effect.

Medical benefits

Although a vaccine is not yet in sight, recent discoveries have raised an interesting conundrum: rather than simply being agents of disease, it appears that parasitic infections, including schistosome worms, may bring medical benefits. Scientists in Cambridge are leading the field in efforts to find out just what is going on.

As more knowledge of the host–parasite relationship is gained, it is becoming increasingly clear that parasitic infections are not necessarily pests that need to be eradicated. Nobody used to have any sympathy for leeches or maggots, but both creatures are now used in medical settings: leeches to clear blood from congested tissues after surgery, and maggots to liquefy dead tissue and kill harmful bacteria in infected wounds. ̽��ֱ��same thing is now happening to parasites, as it emerges that their influence on the immune system can benefit both host and parasite.

In the Department of Pathology, a clear example of this win–win scenario was demonstrated when researchers in Professor Anne Cooke’s group prevented type 1 diabetes from developing in mice by injecting them with antigens of schistosome parasites. This is likely to be due to the same skewing and downregulation of the host immune response described above.

It seems that by diverting and subverting the immune response, schistosome parasites may prevent the immune system from over-reacting to other proteins. One hypothesis gaining popularity is that, when parasites are removed, the immune response finds new targets, either in harmless allergens (leading to allergy), or in the host itself (leading to autoimmune diseases such as type 1 diabetes).

With such tantalising evidence, it may be time to look at the parasite hit-list with fresh eyes, and ask: can we exploit the intimate relationship parasites have with humans at the same time as reducing their tremendous burden on affected populations?

̽��ֱ��Matangini Project

̽��ֱ��Matangini Project was created by Dr Mark Booth, in the Schistosomiasis Research Group at the Department of Pathology, to raise funds for community projects in Kenya and Uganda. ̽��ֱ��aim in 2007 is to raise £5000 to bring safe water to thousands of school children in areas of Kenya affected alternately by drought and water-borne infections such as schistosomiasis.

Cambridge Infectious Disease Initiative

̽��ֱ�� ̽��ֱ�� of Cambridge is currently developing a major Infectious Disease Initiative, with the aim of increasing the ̽��ֱ��’s contribution to reducing the global impact of infectious diseases. By building new partnerships based on core strengths, the vision is to establish the ̽��ֱ�� as a leading international centre for infectious disease teaching and research.

For further information, please contact the Co-ordinator Dr Gill Rands (gfr21@cam.ac.uk).

For more information, please contact the author Dr Mark Booth (mb350@cam.ac.uk) at the Department of Pathology (www.path.cam.ac.uk/~schisto).

̽��ֱ��common view has been that parasitic infections cause disease and must be eliminated. But can we live without them?

As more knowledge of the host–parasite relationship is gained, it is becoming increasingly clear that parasitic infections are not necessarily pests that need to be eradicated.

Max0rz from Flickr

Flatworm

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.

Yes