Office of Technology Transfer – University of Michigan

Biomarker for Chronic Diarrhea Associated with Irritable Bowel Syndrome

Technology #4920

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Categories
Researchers
Juanita L. Merchant
Managed By
Ed Pagani
Assistant Director, Health Technologies 734-763-3558
Patent Protection
US Patent 9,732,387
Publications
Identification of a functional TPH1 polymorphism associated with irritable bowel syndrome bowel habit subtypes.
Am J Gastroenterol. 2013 Nov;108(11):1766-74. doi: 10.1038/ajg.2013.304. Epub 2013 Sep 24., 2013

Irritable bowel syndrome (IBS) is a functional disorder of the intestine affecting the normal motility. IBS is characterized by abdominal pain and altered bowel habits in the absence of an obvious pathology. Based on bowel patterns, IBS can be subtyped into IBS-D (diarrhea predominant) or IBS-C (constipation predominant). Due to the limited knowledge about IBS pathogenesis, there is currently no cure and therapeutics focus on symptoms management. There are 12.7 million IBS patients, with an average annual cost of therapy of $3,882. IBS-D patients experience altered gut motility with more frequent bowel movements and shorter colonic transit times, leading to increased occurrence of diarrhea. 5-HT (or serotonin) is a key paracrine modulator of gastric motility. 5-HT is synthesized in enterochromaffin cells via the rate-limiting enzyme tryptophan hydroxylase 1 (TPH1). Alterations to 5-HT levels are believed to play a role in altered bowel habits in IBS. Abnormally high levels of 5-HT are seen in IBS-D patients. Promising therapeutic developments have been shown for IBS symptom relief by targeting 5-HT levels via inhibition of the rate-limiting enzyme TPH1.

Descriptive Heading based on Block 2 text

A proximal promoter single nucleotide polymorphism (SNP) of TPH1 in IBS patients has been identified. This SNP is proposed to be a marker of IBS-C versus IBS-D. Analysis of DNA from IBS-D and IBS-C patients showed that the IBS-D group had a homozygous C(G) allele nearly twice as often as those with the A(T) allele. Diagnostic testing of patients with IBS for this SNP could identify those that may respond well to treatments targeting TPH1.

Applications

  • Diagnosis of IBS-D and possibly other gastrointestinal disorders

Advantages

  • Non-invasive
  • No currently marketed IBS-D versus IBS-C tests
  • Limited IBS diagnostic testing currently available