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Finding New Avenues of Treatment or Cure
CHORI Scientist Receives Three-Year Crohn's and Colitis Foundation of America Grant

July, 2013 – CHORI Senior Scientist Julie Saba, MD, PhD, has just received a Crohn's and Colitis Foundation of America (CCFA) Senior Research Award to investigate the role of sphingosine-1-phosphate (S1P) in inflammatory bowel disease (IBD) and inflammation-induced colon cancer. The CCFA dedicates itself to finding cures for IBD, and is at the forefront of research in Crohn's disease and ulcerative colitis. Committed to funding cutting-edge studies at major medical institutions, the CCFA provides established researchers with funding for the early foundational research required to garner future grants from the National Institutes of Health (NIH). Already a nationally renown expert in S1P research, Dr. Saba will be undertaking the three-year study to determine for the first time how S1P might contribute to IBD.

"Our research has shown that S1P plays a key role in the overall regulation of inflammation, which can promote the development and progression of cancer, especially in the colon, but also in other forms of cancer," says Dr. Saba. "I'm incredibly pleased to have the opportunity to work with the CCFA to confirm the role of S1P in IBD, and whether or not suppressing S1P could provide a new avenue of therapeutic treatment for pediatric patients with IBD, who are at high risk of developing colon cancer later in life."

“I'm incredibly pleased to have the opportunity to work with the CCFA to confirm the role of S1P in IBD, and whether or not suppressing S1P could provide a new avenue of therapeutic treatment for pediatric patients with IBD.”

IBD is a complex disease caused by the disruption of the immune system's ability to maintain a healthy balance between the gut's mucus lining and the gut's environment, with the end result being chronic inflammation in the colon. Patients with IBD suffer from a variety of symptoms including abdominal cramping and diarrhea, and in some cases, colon cancer. There are currently no cures for IBD, and in severe cases, the entire colon must be removed. S1P, however, is a sphingolipid signaling molecule that has shown significant promise as a potential target for new IBD therapies.

"S1P stimulates inflammation by activating two proteins that are linked to IBD through genetic research, but the exact role of S1P in the development of IBD is poorly understood," says Dr. Saba.

In addition, no one has explored the role of the enzyme, S1P lyase (SPL), which is responsible for breaking down S1P and has the potential to limit the inflammation caused by S1P activation.”
The newly funded CCFA study will provide Dr. Saba with the opportunity to explore whether or not SPL can suppress gut inflammation by maintaining low levels of S1P in intestinal tissues, and whether or not S1P suppression results in the suppression of IBD. In addition, Dr. Saba will investigate whether or not plant-derived sphingolipids found in soy, called sphingadienes (SDs), could provide a protective dietary antidote to S1P, and thus, IBD.

“Our hope is that we will be able to demonstrate that SDs are helpful in the prevention and treatment of IBD, and thus have potential as a therapeutic and/or preventive agent in IBD,” says Dr. Saba, who has already conducted similar studies showing SDs provide a protective benefit in relation to colon cancer.

Finally, Dr. Saba will also investigate whether or not plasma S1P will correlate with IBD diagnosis and disease activity.
"We hope to be able to identify specific S1P-related biomarkers that can help patients in two ways," says Dr. Saba. "The first is that these biomarkers could be used to establish standard laboratory tests that can follow patients' disease activity and prognosis by tracking their intestinal inflammation, and the second is to provide potential targets for novel therapeutic interventions, including but not limited to SPL upregulation by SDs."

The end result of the grant will be three-fold: to gain a better understanding of the cause of inflammation in IBD and confirm the role of S1P; to determine if SDs can suppress S1P and inflammation by increasing SPL levels through simple dietary means; and to develop better laboratory tests and novel treatment protocols.

“Ultimately we want to be able to help doctors provide better care to patients with IBD and to find safe dietary treatments that might prevent or lessen the symptoms of IBD and reduce the risk of colon cancer,
especially in children,” says Dr. Saba.

"In addition, there are already a number of drugs targeting S1P signaling that are being developed and tested in clinical trials for other kinds of autoimmune diseases. We believe that new knowledge gained from these studies could quickly translate into clinical trials in the future and have a meaningful impact on patients with IBD."


Thursday, July 25, 2013 12:00 PM

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