Engineering New Treatments for Celiac Disease

This month’s Gastroenterology featured two new approaches for the treatment of celiac disease.

CP Kelly et al. Gastroenterol 2021; 161: 66-80. Full text: TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study

IS Pultz et al. Gastroenterol 2021; 161: 81-93. Full text: Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease

In the first study, Kelly et al used TAK-101 nanoparticles in Phase 1 and Phase 2a trials. In the Phase 2a trial with 33 patients, TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (−0.63, P = .002), but not in the TAK-101 group (−0.18, P = .110) Overall, TAK-101 was well tolerated and prevented gluten-induced immune activation.

Graphical abstract from CP Kelly et al. Gastroenterol 2021; 161: 66-80.

In the second study, Pultz et al developed TAK-062 which is a novel, computationally designed endopeptidase to break down gluten under simulated gastric conditions in vitro and in healthy participants in the phase I study.  Residual gluten (collected through gastric aspiration in the phase I study) was quantified using R5 and G12 monoclonal antibody enzyme-linked immunosorbent assays. Key finding: In vitro, TAK-062 degraded more than 99% of gluten (3 g and 9 g) within 10 minutes. In the phase I study, administration of TAK-062 was well tolerated and resulted in a median gluten degradation ranging from 97% to more than 99% in complex meals containing 1–6 g gluten at 20–65 minutes postdose.

The associated editorial highlights these studies and reviews their limitations; in addition, the authors review the current non-dietary strategies (see below), pg 21-24: Full text: The Promise of Novel Therapies to Abolish Gluten Immunogenicity in Celiac Disease

From editorial, Gastroenterol 2021; 161: 21-24.

My take: These studies indicate that non-dietary treatments may be effective at some point, but not in the near future.

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