U of T researchers isolate gene for Crohn's disease

IBD Patient Community ^ | April 11, 2004

[Jeff Chandler]

 

 

Public release date: 11-Apr-2004


Contact: Elaine Smith
elaine.smith@utoronto.ca
416-978-5949
University of Toronto

U of T researchers isolate gene for Crohn's disease

 

Researchers at the University of Toronto have isolated a gene that predisposes people to Crohn's disease.

"Isolating this gene is a critical step towards improved diagnosis of this disease and developing better therapies for Crohn's sufferers," says Katherine Siminovitch, a U of T professor with the Department of Medicine. She is also a senior scientist at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital and a founding scientist at Ellipsis Biotherapeutics Corp. "There's an urgent need for better treatment for patients with Crohn's."

Crohn's disease is an inflammatory bowel disease and its prevalence is increasing in industrialized nations. Existing treatments are considered unsatisfactory, often requiring recurring hospitalization and surgeries. Using DNA samples from family groups, Siminovitch and her research team employed a technique called positional cloning to first locate the chromosome containing the gene and then identify the gene. Their findings appear online April 11 in Nature Genetics (www.nature.com/ng/).

The gene isolated by the researchers produces a protein that sits on the cell surface and regulates how substances enter and exit the cell. In a majority of Crohn's disease patients, this protein functions improperly and allows toxins easier access to the cell.

The ability to test for this protein malfunction will help physicians distinguish between Crohn's disease and ulcerative colitis, the other major form of inflammatory bowel disease known. The malfunction is not present in ulcerative colitis, so this gene alteration provides a diagnostic test to help distinguish between the two diseases. Siminovitch says that this information can also be used to diagnose Crohn's disease at an earlier stage and to develop new approaches to treatment. She and her fellow researchers are now working on the development of a chemical that would alter the protein to restore its normal function.

Their findings should shed additional light on the basic causes of chronic inflammation, knowledge that will be invaluable to researchers. "The inflammatory processes that lead to disease are very similar in many chronic, common conditions, such as Crohn's diseases and rheumatoid arthritis, even though the target organ may be different," Siminovitch says.

Ellipsis Biotherapeutics is currently investigating the mutant protein's effects on cell function to with the eventual goal of developing of therapeutics.

However, Siminovitch says there is still much more work to be done in understanding Crohn's disease. "This isn't the only gene involved in Crohn's disease and there are also disease-causing interactions between genes and environmental factors, about which we know very little," she says. "If we can identify the majority of the genes involved in this disease, we can learn how these genes act together to cause disease. This information will help us identify potentially preventable environmental triggers as well."

Other U of T researchers were Bill Newman, David Cescon and Gordon Greenberg, (also at Mount Sinai Hospital), Laurence Rubin (also at Ellipsis and St. Michael's Hospital), Anne M. Griffiths (also at the Hospital for Sick Children) and Vanya Peltekova and Peter St. George-Hyslop (also at Ellipsis). Richard Wintle and Mark Van Oene of Ellipsis Biotherapeutics and Christopher Amos, Qiqing Huang and Xiangjun Gu of the University of Texas also contributed to the research.

 

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CONTACT:

Katherine Siminovitch
Department of Medicine
416-586-4692 or 416-586-8723
ksimin@mshri.on.ca

Elaine Smith
U of T Public Affairs
416-978-5949
elaine.smith@utoronto.ca

[MamaB]

I sure hope this works. This is one of the health problems that caused the death of our younger daughter this year. It is a terrible disease which affects the whole family of a person with it. My nephew's daughter who is about 16 has also been told she has it.

[Jeff Chandler]

I am so sorry about your daughter. There is no way I can know your grief, but I got a small taste of it a few weeks ago. Our 15-year-old daughter, who was just diagnosed with Crohn's, almost died from the bleeding. She was given a 50% chance at the time. An emergency resection saved her life.

She is home now, in remission. I pray that she will never have a flare up like that again.

[Jeff Chandler]

More hope: http://www.freerepublic.com/focus/f-news/1122850/posts.

[templar]

Crohn's disease is an inflammatory bowel disease and its prevalence is increasing in industrialized nations.

If it's genetic in origin, I wonder why it's increasing in industrial nations?

[L`enn]

Could it be possible that industrialized nations have the ability to diagnose it properly? In New Guinea or Angola it is probably called demon possession.

[Jeff Chandler]

There might be a slight genetic disposition to Crohn's, perhaps 20%.

One theory is the Hygiene Theory. We have become so hygienic that our bodies no longer carry the biological "contaminants" which our immune systems are designed to deal with, so they attack our own bodies.

[Jeff Chandler]

It was first diagnosed among Jewish people in New York in the 1930s. It then spread to the general poplulation in the northern states, then to the south, following the pattern of urbanization. It followed a similar pattern in Europe.

[sinkspur]

Your daughter has Crohn's?

Well, my youngest brother died eleven years ago from Colon Cancer as a result of Ulcerative Colitis, a dreaded cousin of Chrons.

These Gastroentero diseases are silent killers, and they are taking from us some of our youngest and most productive people.

My brother had a miserable life, from the time he was 18, until he died at 38.

[Jeff Chandler]

My mistake, it's Hygiene Hypothesis. You can find out more HERE.

[templar]

Thanks for the link, it's interesting. I hadn't heard of this before.

[Jeff Chandler]

May your brother rest in peace.

There are many powerful medicines available now which weren't when your brother was diagnosed, with even more promising treatments on the horizon.

We pray we can keep Elizabeth healthy long enough for some of these treatments to come on line.

[Jeff Chandler]

The results of the trials can be found by following the link on post #4.

[Maven]

I'm so sorry about your daughter. I have a cousin with Crohn's, and a coworker's son suffers from it, as well.

There is a website for a diet that helps people with Crohn's, IBS, Ulcerative Colitis, Celiac Disease and other digestive disorders:

The Specific Carbohydrate Diet

Don't be fooled - this is not a low-carb diet (although it can be adapted for that).

Maven

[Jeff Chandler]

Thank you for the web site. I've bookmarked it.

[FlyVet]

I have a sister in law who has this disease. She is now in her mid 40's, and has constantly struggled with severe health problems. In spite of all that, she is an academic achiever and a school teacher. I don't know how she does it, but she does.

[L`enn]

My comment was based on my knowledge of a "cousin" to Crohn's, Ideopathic Pseudo-Bowel Obstruction, which my son has. It started "surfacing" in the mid-70's. The theory on why it "surfaced" was that since it was present from birth, many infants died for malnutrition (actually a symptom is malapsorption) that was laid to "colic" or other old wives tales of the era. This condition, like many others, takes a long time, sometimes years to diagnose, as other conditions are ruled out by process of elimination before they settle on it. Before the prevelance of hyperal and lipid (TPN) many children wasted away before it was even known what it was. Now children can survive this and it would appear that the condition is on the upsurge, when in fact its because medical science is making them able to survive when it was not possible before.

[Jeff Chandler]

Ideopathic Pseudo-Bowel Obstruction

Does that mean they don't know what is causing it, but are treating the symptoms? Does he still suffer from it? How are they treating it?

[L`enn]

Jeff,

It could be neurological, it could be muscular. They do not know. Genetic, probably, but again who knows. Hence the ideopathic tag. In short his intestines , specifically the peristalsis and the nutrition absorption, do not work properly. Sometimes they do, most the time they don't. The spot that does not work changes locations. Its a strange one.

He has an ostomy now. He received that after going in to surgery for a G-tube. The colon was so huge the doctor changed direction in midstream (with our consent of course), did a resection and put in an ostomy, to give his bowel a rest. One of the other symptons is mega-colon (which that was) and a large bladder (causing urine retention and repetitive UTI's.

He is basically treated by TPN to give him nutrition and electrolytes. He had 4 hospitalizations in the last year for electrolyte imbalances. Again why? Who knows. Could be the growth into a teenager. He eats and has hunger but gets little or no nutrition form it due to the malrotation.

Despite all of this you would not believe how close to normal he is. He does not bemoan his condition, accepts everything. He misses a lot of school thats a huge drawback. I always worry about social acceptance, but he is a great looking , sassy kid and he will not take any crap from anyone. If you saw him you would not guess a thing is wrong. I guess it is because he had it from birth and it is all he knows. I see the posting before about the child that had the onset of Crohns at 11. That had to be 100 percent more difficult because that was a lifestyle change. Steven (my son) has had no lifestyle change. It is what it is , and he deals with it.

Thanks for asking Jeff.

Lenn

[Malsua]

Very interesting.

I grew up with a friend that didn't have it until he hit about 18. He grew up on a 400 acre farm and raised Pigs, cows, sheep, chickens, rabbits, etc.

As he got into his later teens, he stopped doing much farm work. The hygene thing strikes me as almost peg on to his situation. After he left his family farm, Crohns got worse and worse. I've not spoken with him in 5 years or so now(I left the state), but I do email his brother in law. I'm going to forward this article to him. Thanks.