A Unique Approach
IBS patients suffer recurrent intermittent pain attacks described as having a sudden onset with an intensity over and above any background pain level. These pain attacks typically occur about twice per week and last for longer than 30 minutes and usually for many hours. A significant number of patients seek pain medication and/or go to bed. About 18% take opioids. No pain medication is specifically indicated for these patients.
GLP-1 is mainly secreted by specific cells in the small intestine, but it is also secreted in the pancreas and the brain. It has direct effects on the GI tract, the regulation of food intake and glucose homeostasis, and the perception of visceral pain. It delays gastric emptying by vagus nerve mediated pathways, which slows down the rate at which food passes from the stomach to the small intestine, reducing the post-prandial glycemic load. It also relaxes GI muscle activity, slowing small bowel transit, but without significantly affecting colonic transit. Recent studies have shown that it blocks pain hypersensitivity, but not the acute nociceptive response.
GLP-1 acts through binding at cell receptors which are located in the pancreas, the brain, vagus nerve, and the dorsal root ganglia, muscle and other tissues. The effect of GLP-1 on smooth muscle and its role in IBS is not completely understood. However, in women with IBS-C, there is both a decrease in serum GLP-1, and a decrease in colonic GLP-1 receptor expression, which is inversely correlated with pain intensity.
Native GLP-1 has a very short half-life, which limits its utility as a drug. Synthetic forms of GLP-1 have been used to treat diabetes for over a decade, either by delaying gastric emptying in the case of shorter half-life products, or by increasing insulin secretion in the case of the longer acting ones.
ROSE-010’s pharmacokinetic properties are ideally suited for a pain indication because it’s very close to native GLP-1 in structure (97%), which allows a more rapid onset of effect than the analogues designed for diabetes.