Targeted enzymatic therapy for coeliac disease - PubMed
3 hours ago
- #enzyme therapy
- #celiac disease
- #gluten degradation
- Celiac disease (CD) is an autoimmune enteropathy triggered by proline-rich gluten immunogenic peptides (GIPs), with no curative therapy.
- Researchers developed celiacase (Clc), a recombinant prolyl endopeptidase engineered from pitcher plant neprosin to improve expression, stability, and activity.
- Clc showed maximal activity at gastric pH, resisted pepsin, and efficiently degraded GIPs, including the highly immunogenic 33-mer, outperforming other enzymes like Aspergillus niger prolyl endopeptidase.
- In a dynamic human gastrointestinal simulator, Clc reduced GIP levels by up to 99% at an enzyme-to-gliadin ratio of 1:250.
- Ex vivo tests showed Clc-digested 33-mer fragments did not elicit cytokine responses in mouse and rat macrophages or duodenal biopsies from CD patients.
- In vivo studies in gliadin-fed mice demonstrated that low-dose Clc degraded gliadin, reduced villus atrophy, inflammation, antibody responses, and gluten-induced dysbiosis, while restoring immune-regulatory markers and microbial metabolic pathways.
- Clc is a potent, acid-stable glutenase with potential as a therapeutic adjunct or alternative to a gluten-free diet for CD patients.