Therapy is designed to block PAI-1, a mediator of inflammation, fibrosis by Patricia Inácio, PhD | June 18, 2024 The first healthy volunteers have been dosed in a Phase 1 clinical study that’s evaluating MDI-2517, a small molecule candidate to treat scleroderma and interstitial lung disease (ILD), which occurs when the lungs become scarred. According to developers MDI Therapeutics, MDI-2517 is a potent blocker of plasminogen activator inhibitor-1 (PAI-1), a protein and key mediator of inflammation and fibrosis, or tissue scarring and thickening. “Based on comprehensive preclinical studies, this first in-human study of MDI-2517 will inform continued development of our novel, proprietary compound for the potential treatment of systemic sclerosis and interstitial lung disease, conditions where disability is significant and survival rates are poor,” Mark Weinberg, MD, chief medical officer at MDI Therapeutics, said in a company press release. In scleroderma, a self-reactive immune system causes fibrosis in the skin and possibly in internal organs, including the heart, kidney, lungs, and digestive tract. The disease is thought to develop due to a combination of genetic and environmental factors, resulting in the attack of body tissues by so-called autoantibodies. How would MDI-2517 work?
While PAI-1 is important in wound healing, its overactivation leads to fibrosis by promoting the production and deposition of collagen protein. PAI-1 also promotes inflammatory cells to infiltrate tissues, such as the lungs. In preclinical studies, MDI-2517 lowered PAI-1 to that seen in normal, physiologic conditions, according to MDI. The Phase 1 trial (NCT06453824), which is going on at a single center in Florida, is testing single ascending doses of MDI-2517, given once as an oral tablet, against a placebo. Up to 48 healthy participants, age 18-55, are being enrolled. The candidate’s safety and tolerability are being tested, and the study will evaluate its pharmacokinetics, or how it moves into, through, and out of the body. Its pharmacodynamics, that is, the effects of a compound on the body, and changes in the total and active levels of PAI-1 also will be assessed in exploratory analyses. “Beyond these initial indications [scleroderma and ILD], the outcomes of the Phase 1 trial will also support the potential evaluation of MDI-2517 in other chronic fibrotic and inflammatory diseases that have been associated with excessive PAI-1 activity,” Weinberg said. Comments are closed.
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AuthorScleroderma Queensland Support Group Archives
December 2024
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