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New Genetic Discovery May Explain Why Some People With Crohn’s Disease Suffer More

May 26, 2017 - crohns
New Genetic Discovery May Explain Why Some People With Crohn’s Disease Suffer More

More than half a million people in the U.S. suffer from Crohns disease, according to recent estimates, but their experiences with the chronic illness can diverge dramatically and new research changes the thinking on why the disease affects people differently.

Some patients can experience pretty mild disease with relatively little disruption to their lives while others have a really torrid time with severe symptoms and recurrent flare-ups, said James Lee, a gastroenterologist at University of Cambridge and author of a new genetic analysis of people with Crohns.

Indeed, some people may not notice symptoms for years after diagnosis, and others with the disease require courses of aggressive immunosuppressant medications and multiple surgeries, as well as time off from work or disability leave.

While the cause of Crohns is not totally clear, researchers have established that the presence of certain genes more than 170 genes fall into this category along with the presence of some types ofgut bacteria, are linked to a persons risk of developing the disease. Typically, the more of these 170-plus Crohns risk genes a person has, the more likely they are to develop Crohns.

And until now, experts had assumed that people with particularly severe Crohns disease likely carried even more of these genes.But Lee and a team of researchers have identified a completely different set of genetic markers that explain severity: Four genes previously not known to be related to Crohns that appear to determine how severe a case of Crohns will get.

Tracking The Genes That Contribute To Crohns

The researchers analyzed whole genomes of 2,734 individuals with Crohns, identifying four genes that influenced how severe a persons symptoms were, but did not play a role in that persons overall risk of developing Crohns in the first place.

Whats more, none of the 170-plus genes previously linked to Crohns risk seemed to affect the severity of the prognoses, counter to what hadbeen the medical consensus, Lee said.

And the four genes newly connected to Crohns were ones other research had previously found play a role in determining the severity of other chronic conditions, like arthritis and other autoimmune diseases(though they arenot linked to the risk of developing those illnesses either).

That link to other diseases suggests that if scientists are able to design drugs that work against the specific genetic pathways identified in this study, such therapies may be effective on a range of illnesses, not just Crohns, Lee said.

The Future Of Genetic Therapy

A bulk of Crohns research over the past 10 years has focused on how the disease develops rather than how the symptoms manifest.

From a patients (and doctors) perspective, the most important questions [at the point of treatment] are not related to how the disease developed, but rather to what the disease will do over the coming months and years, Lee said via email.

When it comes to treating patients with Crohns, doctors currently start by prescribing strong immunosuppressive drugs to help keep the disease in check. But if those dont work, some patients will require surgery to remove parts of the damaged intestine and some patients go on to have these surgeries multiple times.

We can now focus on developing drugs that actually target relevant pathways which should provide more effective therapies. James Lee, a gastroenterologist at University of Cambridge

By identifying the genes that are involved in determining outcomes in Crohns disease, we can now focus on developing drugs that actually target relevant pathways which should provide more effective therapies, Lee explained.

Such new drugs are still likely a long way off, he added. The next step is taking a closer look at the four newly identified genes to better understand them and then repurpose existing drugs (or design brand-new ones) to specifically target the parts of those genes that cause Crohns to flare up. And once scientists have an idea of what drugs might work, they would need to first be tested in the lab, then in animal models (if possible) and then in multiple phases of clinical trials in people.

But for the doctors and scientists actually investigating how to better help people with Crohns disease, Lee said: This work represents a major step forward.

This reporting is brought to you by HuffPosts health and science platform, The Scope. Like us onFacebookandTwitterand tell us your story:scopestories@huffingtonpost.com.

Sarah DiGiulio is The Huffington Posts sleep reporter. You can contact her at sarah.digiulio@huffingtonpost.com.

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