Christchurch microbiologist may have cracked Crohn’s disease, The Press

Martin van Beynen, The Press,  21 May 2016

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Research by Christchurch microbiologist John Aitken has recorded a major advance in the treatment of Crohn’s disease, which affects 20,000 New Zealanders. Martin van Beynen reports.

 

A scientific breakthrough at a Christchurch laboratory could help researchers find a cure for Crohn’s disease.

 

Crohn’s causes rectal bleeding, diarrhoea, lethargy and weight loss. It affects about 20,000 New Zealanders and is on the increase.

 

Clinicians and scientists have for decades been divided on whether Crohn’s is caused by bacteria or a defect in the immune system. Current treatment relies mainly on immuno-suppressant drugs and steroids.

John Aitken, microbiologist and Director, Otakaro Pathways
John Aitken, microbiologist and Director, Otakaro Pathways (Photo by Iain McGregor, FairfaxNZ)

Christchurch microbiologist John Aitken and his team at Otakaro Pathways Ltd have been able to make the organism which many argue is the bacteria causing Crohn’s visible under a microscope and grow it in culture.

 

With further development of the test, scientists will be able to see how the bacteria reacts to therapeutics and observe how it works.

 

‘‘If it is all correct, it does signal a huge change,’’ Aitken said.

 

Christchurch gastroenterologist Professor Richard Gearry, who has worked with Aitken on previous studies, said scientists have struggled to grow the bacteria and ‘‘nobody has had the same sort of success and length of success at being able to do that as John’’.

 

Techniques developed by Aitken mean laboratories will be able to see how the organism responds in cell cultures similar to those seen in Crohn’s patients, he said.

 

The research could lead to treatments for Crohn’s disease in livestock and more effective therapies for other auto-immune diseases like multiple sclerosis.

 

Aitken said the development could also result in the discovery of new antibiotics as big pharmaceutical companies began to see the potential.

 

He doesn’t want to get ahead of himself, though.

 

‘‘I’m just a small cog in the wheel. I’m the guy who has worked out a way of seeing the bug. That still requires things like animal testing and stuff like that to prove it causes Crohn’s. But I’m not in isolation. There are clinicians out there at the moment who are using the therapeutics based on what we are observing. ‘‘The organism is in the blood and lymph nodes. What we have worked out is a way that any laboratory scientist in the world working in a diagnostic lab on the front line can do the test and see it.’’

 

It was still a big step to say the organism caused Crohn’s, he said, although he suspected it did. For Christchurch chef and Crohn’s sufferer Ryan Henley, the research advance is ‘‘good news’’.

 

‘‘I would love there to be a cure for Crohn’s. I’ve dealt with it for nearly 10-11 years and it’s part of my life. I just deal with it. But I have a threeyear-old daughter who I would hate to get it.’’

 

Henley was only 21 and head chef at the Pescatore restaurant at the George Hotel in Christchurch when he began getting stomach pains, feeling very tired and losing weight.

 

He put it down to working too much and doing too many competitions. It took four years for Crohn’s to be diagnosed. By then he had a hole in his bowel and needed surgery.

 

‘‘I realised I had to change my lifestyle and how I eat and live.’’

 

He now works at Maddisons restaurant in the Heritage Hotel and is starting his own restaurant in a few weeks. A good diet and exercise are vital to his health and he also receives an injection of the immuno-suppressant drug Humira every two weeks. The drug is working well but leaves him vulnerable to other infections.

 

‘‘You get sick quite easily. But I would rather deal with that than ongoing Crohn’s.’’

‘‘I’m just a small cog in the wheel. I’m the guy who has worked out a way of seeing the bug.’’

John Milford Aitken was the sort of kid who wanted a microscope for Christmas. He was a bright boy with a scientific bent growing up in Hornby in a working-class household.

 

His father, a freezing worker, and mother, a housewife, were happy to encourage the interest and, after high schooling at Christchurch Boys’ High, he began training in medical technology at the Christchurch Hospital pathology department in 1970.

 

Although not university educated, he has since had a stellar career in microbiology, managing several laboratories and setting up his own. He is now 65, financially comfortable and would probably have slowed down but for one thing.

 

He calls them Crohn’s mothers and he feels their nagging, desperate presence when he looks down his microscope. They need answers and Aitken and his team have put Christchurch at an important front in the attack on the disease by mastering a difficult test that could lead to a cure.

 

Crohn’s is a devastating and currently incurable condition in which the intestinal tract becomes inflamed. Sufferers experience rectal bleeding, diarrhoea, nausea, pain, fever and weight loss. In bad periods, a thing doctors call ‘‘faecal urgency’’ requires people with Crohn’s to always be near a toilet. Some need serious surgery and end up with a colostomy bag. They have a greater risk of bowel cancer.

 

The prevalence of the disease is increasing worldwide. Findings from a study in Canterbury, for instance, show the rate of Crohn’s increasing from 16.5 per 100,000 in 2004 to 26 per 100,000 in 2014.

 

The underlying cause of the disease remains murky. The prevailing theory is that Crohn’s is caused by the immune system responding strangely to something in the gut environment of people with the wrong genes. Clinicians have had results with drugs suppressing the immune system but the therapy is certainly no cure and patients are crying out for something better.

 

Bacteria as cause

Other clinicians and scientists suspect the cause of Crohn’s is a form of bacteria that causes inflammation and can be eradicated with a specific cocktail of antibiotics.

 

The most likely pathogen if Crohn’s is caused by bacteria is Mycobacterium

 

avium subspecies paratuberculosis (MAP), which causes Johne’s disease in livestock and has remarkably similar symptoms to Crohn’s in humans.

 

Humans are believed to get infected through milk and meat products and can generally cope. It’s thought Crohn’s patients have a defect that allows MAP to attack the intestines.

 

Numerous studies have shown MAP is more prevalent in Crohn’s patients but the question is whether it is a cause or merely present as a bystander in the disease.

 

Success experienced by clinicians using antibiotics tends to support a bacterial cause, but mainstream gastroenterologists want more proof.

 

This requires researchers to be able to grow or culture the organism MAP – or a variant – in the laboratory. Italian scientist Rod Chiodini managed it in 1984 by isolating a mycobacterium found in three out of 11 Crohn’s patients. It took him 18 months and other labs find it almost impossible to repeat his work.

 

This is where Aitken and his team comes in. His laboratory has not only isolated and grown the mycobacterium thought to have a role in Crohn’s but has also developed a technique to make it visible. Even though the process is difficult, his technique takes only 10 days and has been repeated at a laboratory in Australia.

 

Christchurch gastroenterologist Professor Richard Gearry, who has worked with Aitken on previous studies, says scientists have struggled to grow the MAP-type bacteria and ‘‘nobody has had the same sort of success . . . as John’’.

 

‘‘If you can grow it, you can start to explore causation a lot more. Not only that, but that work will translate to Johne’s disease in livestock which is a big problem in NZ.

 

‘‘People internationally are very interested in that. All of sudden you can get underneath the clinical observations and try and understand those mechanisms as to what is going on.’’

 

Early brush with Crohn’s

Aitken became interested in Crohn’s as a 23-year-old when he was told he had it. He spent the next three years with an image of his colon snapping like a carrot.

 

It turned out he did not have Crohn’s, but his brush with the disease sharpened his interest.

 

In 2005, a US colleague, whose wife had Crohn’s, asked him to look at her blood samples and he was able to see the elusive mycobacterium associated with Crohn’s under the microscope.

 

By 2010, he was able to grow the bacteria and Crohn’s clinicians and researchers were starting to take notice.

 

A year later, Aitken and others set up a medical laboratory under the banner of Otakaro Pathways Ltd in the old Princess Margaret Hospital mortuary. Funding came from various sources including Callaghan Innovation.

 

Canterbury’s earthquakes intervened, but Aitken is pushing ahead with his research with renewed vigour and setting up a new laboratory in the Templeton Industrial park.

 

One of the shareholders is Professor Tom Borody, who runs the Centre for Digestive Diseases in Sydney. He is a controversial figure in his field, but since he invented using antibiotic therapy against the bug that can cause stomach ulcers, he is not taken lightly.

 

Borody doesn’t need more testing to be convinced Crohn’s is bacterial in origin. He is well known in Australia as a gastroenterologist prepared to treat Crohn’s with a cocktail of antibiotics which Aitken says are achieving 80 to 90 per cent remission rates.

 

While patients are queuing up to see Borody, the medical world is not exactly beating a path to his door.

 

‘‘It’s very difficult for experts to prove themselves wrong,’’ says Aitken, who doesn’t want to be pigeonholed as a bacteria advocate, although it’s clear where his research places him.

 

He avoids calling the organism he has grown and made visible MAP.

 

‘‘What we are trying to do is have a test out there that can tell whether therapy against the mycobacterium is working.’’

 

If researchers find out that mycobacteria cause Crohn’s and discover how the mechanism works, the key to curing or treating other diseases like multiple sclerosis might be next.

 

A raging debate

For the moment, mainstream gastroenterologists like Gearry will not prescribe the cocktail favoured by Borody to Crohn’s patients even if they want them.

 

He describes the immune system versus bacteria Crohn’s debate as ‘‘incredibly polarising’’.

 

‘‘A lot of groups around the world are very strong in using this anti-MAP therapy. They all zealously believe MAP is the cause . . . but the concern is maybe they can’t afford to see [their hypothesis] fail and there are financial interests in it as well.’’

 

Gearry says the best test of anti-MAP therapy so far was a randomised control trial in Australia involving about 200 patients who were given the three antibiotics Borody and others claimed were the key to treating Crohn’s.

 

Those running the trial, the methodology of which was later criticised, concluded the anti-MAP therapy was no more effective than a placebo.

 

The results did not discourage large Israeli pharmaceutical company Redhill from funding another randomised control study which got under way this year. Redhill developed a pill which combines the three antibiotics – Clarithromycin, Rifabutin and Clofazimine – used by Borody.

 

Gearry is supervising the trial in Canterbury and so far has two patients taking part.

 

‘‘I have no opinion on it. What I have been really worried about is the science behind what has gone on with the clinical aspects of this. It hasn’t been rigorous and it’s been led by people other reasons for it to succeed.’’

 

Aitken’s legacy

The results of the trial are keenly awaited internationally.

 

Meanwhile, other Crohn’s research groups around the world are making strides into aspects of Crohn’s. Aitken, for instance, is working with a group in Bulgaria. The race is on.

 

Aitken hasn’t published his work for fear of it being pinched. He not quite ready to tell the world. He certainly doesn’t need more money.

 

‘‘Instead of going in with circumstantial evidence, you are much better going in with total forensic evidence.’’

 

Aitken comes back frequently to the patients and their mothers.

 

‘‘The mothers of the children are just unbelievable. I’ve never seen anything like it. It’s like they sense there is something out there they must reach it whatever it takes.’’

 

They send him cards, drawings and letters of thanks.

 

He is not about to let them down and would dearly love his legacy to be a major contribution to making life better for Crohn’s sufferers.

 

‘‘If you can grow [MAP-type bacteria], you can start to explore causation a lot more. Not only that, but that work will translate to Johne’s disease in livestock which is a big problem in NZ.