Gila is focused on pharmacological treatment of obesity, and related metabolic diseases, employing intra-oral application of naturally occurring satiety hormones. We are driving to demonstrate that this induces early fullness, and potentially leads to weight loss. Targeting a unique and recently discovered direct neural pathway between the tongue and brain, Gila is developing formulations that when applied to the tongue prior to meals are believed to directly stimulate the brain’s satiety centers without significant systemic exposure.
Since early 2016, we have moved rapidly and efficiently to drive GT-001 from concept into clinical studies. We have successfully completed our initial Phase 1 clinical trial, and are poised to start our second clinical study.
About Peptide YY3-36 (PYY3-36)
Peptide, PYY3-36 is a satiation gut hormone released postprandially mainly by the gut. Its secretion is related to caloric intake and induces satiation through several signaling pathways, ultimately inhibiting the NPY/AgRP pathway via Y2 receptors in the arcuate nucleus of the hypothalamus. Recently, we found that this hormone is present in human and murine saliva where its concentration follows its plasma level (Acosta et al., 2011). In mice, topical intraoral PYY3-36 application was found to induce earlier and higher satiation, as demonstrated by feeding behavioral studies and by c-Fos activation in the arcuate nucleus of the hypothalamus.
Interestingly, topical intraoral application of PYY3-36 in mice results in decreased food intake and decreased body weight without stimulating the nausea centers (area postrema) in the brainstem. Furthermore, PYY3-36 applied this way is not significantly absorbed into the blood (systemic), suggesting a local (topical) effect.
Gila’s goal is to demonstrate that topical lingual application of PYY3-36 is effective in increasing satiation without altering taste perception or causing nausea, and without significantly elevating endogenous plasma PYY3-36 levels.
The GT-001 development program employs a systematic approach to test the clinical hypothesis that PYY3-36 can induce satiety with clinically meaningful reduction in body weight. PYY3-36 has been evaluated in both animal studies and human clinical trials. Historically, PYY3-36 has been administered as an intravenous (IV) infusion as well via the nasal mucosa.
Acosta A, Hurtado M, Gorbatyuk O, La Sal, M, Dunca D, Aslanidi G, Campbell-Thompson M, Zhang L, Herzog H, Voutetakis A, Baum B, and Zolotukhin S. Salivary PYY: A Putative Bypass to Satiety. PLoS One. 2011;6(10): e26137. doi: 10.1371/journal.pone.0026137. Epub 2011 Oct 10.