University of Iowa, Illinois partnership leads to clinical testing of novel therapy for cystic fibrosis
Building on decades of foundational research by faculty at University of Iowa Carver College of Medicine and Carle Illinois College of Medicine, a promising new treatment for cystic fibrosis is now being tested in a clinical trial.
Cystic fibrosis (CF) is a genetic disease that progressively destroys the lungs. The lining of CF bronchi is missing the CFTR channel protein, which provides a pathway for salt flow into the airway. The novel treatment uses an inhaled drug to replace the missing CFTR channel with an artificial channel; that is, a “molecular prosthesis.”
The ongoing clinical trial is evaluating the new drug’s safety in a phase 1 study in New Zealand. The treatment is not yet available in the United States. This project is the result of a joint public-private partnership between the UI Roy J. and Lucille A. Carver College of Medicine (UI), the Carle Illinois College of Medicine at the University of Illinois Urbana-Champaign (UIUC), and spin-out biotechnology company, cystetic Medicines.
The new treatment is based on research in the lab of Michael Welsh, MD, a UI professor of internal medicine, and Martin Burke, MD, PhD, a UIUC chemistry professor. Together, they co-founded cystetic Medicines. Welsh serves as the chair of cystetic Medicines Scientific Advisory Board, and Ian Thornell, a UI assistant professor of internal medicine, is actively participating in the development of the potential new drug.
“It takes many people and years of basic research followed by translational work to bring effective new therapies to the public,” says Welsh, a Howard Hughes Medical Institute investigator whose work on the fundamental biology of CF helped lead to treatments that have dramatically improved and extended the lives of people with CF.
"We begin by observing and describing the disease. Then teams of scientists work to uncover the fundamental, cellular mechanisms going awry. With that knowledge, we can begin to develop corrective treatments,” says Welsh.
About 90% of people with CF produce CFTR channels that do not work properly. For these individuals, a class of drugs called CFTR modulators can often restore CFTR channel function and improve breathing. But treatments are limited for people whose bodies produce little or no CFTR.
The first human volunteers recently began taking the new inhaled drug, CM001 (also known as amphotericin B cystetic for inhalation, or ABCI). The approach uses an inhaled dry powder formulation to directly target the lungs.
“With this method, people with CF could directly deliver this molecular prosthetic to their lungs where they need it most, hopefully increasing its efficacy and safety,” says Burke, who leads the cystetic Medicines team.
People with CF have played a crucial role in earlier testing of the new treatment, said Agnieszka Lewandowska, a senior research scientist at Illinois and a member of Burke’s lab.
“We are grateful for the willingness of the CF community that provided cells through the University of Iowa’s Cystic Fibrosis Research Center that ultimately brought these compounds to clinical trial,” Lewandowska said. “In collaboration with laboratories of Mike Welsh and Ian Thornell at the University of Iowa, we were able to demonstrate that ABCI, developed in partnership with cystetic Medicines and UIUC, restores ion channel function to cells from people with CF.”
This research is supported by both the public and private sectors, including a $32 million investment from Deerfield Management and support from Illinois Ventures. The non-profit Emily’s Entourage also provided grant funding for early-stage research by cystetic Medicines. Results of the clinical trial are expected in 2024.