A first-in-human clinical trial of remestemcel-L delivered by an endoscope directly to areas of inflammation and tissue injury in patients with medically refractory Crohn’s disease and ulcerative colitis has commenced.

Mesoblast Limited, which produces the drug, is leading the randomised, controlled study at Cleveland Clinic, US. Remestemcel-L is an investigational therapy comprising culture-expanded mesenchymal stem cells (MSCs) derived from the bone marrow of an unrelated donor. The therapy is thought to have immunomodulatory properties to counteract severe inflammatory processes by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

“Inflammation of the gut in Crohn’s disease and ulcerative colitis closely resembles the most severe manifestation of advanced-stage, life-threatening acute graft versus host disease (aGVHD). Mesoblast’s objective is to confirm the potential for remestemcel-L to induce luminal healing and early remission in a wider spectrum of diseases with severe inflammation of the gut, in addition to steroid-refractory aGVHD,” said Dr Fred Grossman, Mesoblast Chief Medical Officer.

According to the researchers, MSCs promote healing of inflamed gut tissue by downregulating gut mucosal effector T-cell activity and promoting regulatory T-cell formation. The study at Cleveland Clinic will be the first in humans using local delivery of MSCs in the gut and will enable the company to compare clinical outcomes using this delivery method with results from an ongoing randomised, placebo-controlled trial in patients with biologic-refractory Crohn’s disease where remestemcel-L was administered intravenously.

The study’s lead investigator Dr Amy Lightner, from the Cleveland Clinic, stated: “We are aiming to establish a new treatment paradigm by administering remestemcel-L at one of two escalating doses, or placebo, directly to inflamed gut tissue in patients with medically refractory Crohn’s disease and ulcerative colitis, both highly debilitating conditions with significant, unmet medical needs.”