Research Article Details
| Article ID: | A11329 |
| PMID: | 30935932 |
| Source: | Gastrointest Endosc |
| Title: | Duodenal mucosal resurfacing: proof-of-concept, procedural development, and initial implementation in the clinical setting. |
| Abstract: | BACKGROUND AND AIMS: We aimed to develop duodenal mucosal resurfacing (DMR), a minimally invasive upper endoscopic hydrothermal ablation procedure, to treat insulin-resistant metabolic diseases. METHODS: We completed a sham-controlled, rodent proof-of-concept study and longitudinal safety study in pigs to demonstrate feasibility to test DMR in humans. Subsequently, the DMR procedure was implemented in an open-label first-in-human (FIH) study of safety and efficacy in patients with type 2 diabetes (T2D). RESULTS: In rats, duodenal abrasion reduced hyperglycemia by 59 mg/dL on average, compared with no change from baseline in the sham treatment arm (P < .05). In pigs, the balloon catheter successfully and safely delivered hydrothermal ablation to the duodenal mucosa and superficial submucosa. Complete mucosal healing was demonstrated by week 6. In the FIH study, hydrothermal ablation was successfully administered with no evidence of perforation, pancreatitis, or hemorrhage. Duodenal biopsy specimens obtained 3 months postprocedure demonstrated full mucosal regrowth. No inflammation was observed, and there was minimal-to-mild collagen banding deposition observed in a proportion of ablation site biopsy specimens with no evidence of fibrotic scarring. Glycemic and hepatic measures improved through 6 months of follow-up. CONCLUSIONS: DMR shows potential as an endoscopic intervention that improves glycemic and hepatic parameters in patients with T2D. Further mechanistic and clinical studies are underway to further explore DMR as a treatment for metabolic disease. |
| DOI: | 10.1016/j.gie.2019.03.024 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |