Saint Louis University, Dis Industry Partners

ST. LOUIS — Researchers at Saint Louis University School of Medicine, in collaboration with Arrowhead Pharmaceuticals and Takeda Pharmaceuticals, report the first effective drug to treat a rare genetic liver disease previously treatable only with a liver transplant. liver.

The study, “Fazirsiran for liver disease associated with alpha1-antitrypsin deficiency”, was published online in the New England Journal of Medicineone of the world’s leading medical journals.

The Phase 2, open-label, multicenter trial investigated the safety and efficacy of fazirsiran, an RNA interference drug, in patients 18 to 75 years of age with liver disease associated with alpha-1 antitrypsin (AAT) deficiency. AAT is a protein that is made in the liver and released into the blood in large amounts to help protect the body by preventing infection.

Dr Jeffrey Teckmanprofessor of pediatrics and biochemistry and molecular biology, is the lead author of the article.

“This is the culmination of more than a decade of work to cure this disease, and a significant portion of the work was done here,” said Teckman, who is also director of pediatric gastroenterology and hepatology at SLU. “We have patients coming from all over the country to see the knowledgeable SLU faculty members at SSM Health’s Cardinal Glennon Children’s Hospital with this disease for care and to participate in our studies.”

Teckman is a leading authority on AAT deficiency, which affects 1 in 3,500 births and causes severe lung disease in adults or liver disease in adults and children. Symptoms can include shortness of breath and wheezing, repeated lung infections, yellow skin, fatigue, liver cirrhosis, liver failure, and even death.

Teckman says that people affected by the disease often go undiagnosed or are misdiagnosed as fatty liver disease, asthma or smoking-related lung disease. The diagnosis can be suspected by finding low levels of AAT in the blood and confirmed by genetic testing.

“When I was in medical school, I learned that reducing hepatic fibrosis, or scar tissue in the liver, with AAT deficiency was impossible, but now we see that we can reverse this process in humans with minimal side effects,” Teckman said. .

Longtime collaborator Arrowhead Pharmaceuticals used technology during the trial, which allowed doctors to turn off a gene in the human liver with almost no side effects.

“In this case, we chose to shut down the abnormal alpha-1 antitrypsin gene in the liver, and the new drug can effectively do that, stopping the disease and allowing the liver to heal,” Teckman said.

The team will then expand the international study to more adult and pediatric patients in collaboration with Takeda Pharmaceuticals.

Arrowhead Pharmaceuticals supported this work. Strnad is supported by the German Research Foundation (DFG) (grant STR1095/6-1) and the DFG CRC/SFB 1382 “Gut-Liver Axis” consortium (ID 403224013). Teckman is supported by Arrowhead Pharmaceuticals, Takeda, and The Alpha-1 Foundation for this work.

Other authors include Pavel Strnad, MD, Department of Internal Medicine III, University Hospital; Christian Trautwein, MD, Department of Internal Medicine III, University Hospital; Mattias Mandorfer, MD, Ph.D., Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna; Gourab Choudhury, MD, Department of Respiratory Medicine, Royal Infirmary of Edinburgh University Hospital, University of Edinburgh, Edinburgh; William Griffiths, MD, Department of Hepatology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge; Rohit Loomba, MD, Division of Gastroenterology, University of California San Diego School of Medicine; Thomas Schluep, Sc.D., Ting Chang, Ph.D., Min Yi, Ph.D., Bruce D. Given, MD, James C. Hamilton, MD, and Javier San Martin, MD, Arrowhead Pharmaceuticals.

Saint Louis University School of Medicine

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care locally, nationally, and internationally. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.