Use of sustained-release 5-hydroxytrypophan in treating constipation

Unmet Need

Over 10% of the population suffers from constipation disorders, with irritable bowel syndrome-constipation and chronic idiopathic constipation being the most prevalent diagnoses. Current treatment options for constipation are available over-the-counter by prescription. However, in many cases these common treatments don’t work well or have undesired side effects for the individual. Therefore, there is a need for alternative constipation treatments with novel mechanisms of action.

Technology

This technology is a therapeutic formulation for treating constipation. The inventors have reported a sustained release formula of 5-hydroxytryptophan (5-HTP SR). 5-HTP is a precursor to serotonin (5-HT) produced by the enteric nervous system (ENS) and the enterochromaffin cells of the gut. It is well known that supplementation of 5-HTP promotes motility and fluid secretion in the GI tract. However, due to the rapid pharmacokinetics, immediate release 5-HTP is not suitable for treating GI conditions. To demonstrate the utility of 5-HTP SR, the inventors created a mouse model harboring a mutation in tryptophan hydrolase 2 (THP2), the enzyme that converts tryptophan to 5-HTP. These mice showed abnormalities in GI anatomy and function including decreased ENS neuronal number and slow GI transit. Supplementation with 5-HTP increased GI motility and peristaltic contractions in these mice. In addition, supplementation with 5-HTP SR rescued the GI neuroanatomy abnormalities seen in THP2 mutant mice.

Other Applications

This technology may be applicable to other GI disorders including Irritable Bowel Syndrome (IBS), short gut syndrome, postoperative gut repair, functional visceral pain, visceral hypersensitivity and ENS hypoplasia.

Advantages

• A first-in-class treatment for constipation
• Rescued GI neuroanatomy abnormalities in mouse models