News
Florida and Massachusetts researchers report progress in study of potential gene therapy for Alpha-1
University of Florida
GAINESVILLE, Fla. — Researchers have safely given new, functional genes to patients with Alpha-1 Antitrypsin Deficiency, according to clinical trial findings slated to appear this week in the online early edition of the Proceedings of the National Academy of Sciences.
Three patients, apparently for the first time in their lives, were able to produce trace amounts of the protective form of alpha-1 protein for up to one year, a potential step toward a gene therapy for about 100,000 Americans with Alpha-1.
In the study, researchers at the University of Florida and the University of Massachusetts describe how they injected into patients’ upper arms doses of a harmless virus containing copies of the correct gene for alpha-1 protein.
In most people, alpha-1 antitrypsin is made in the liver and protects the lungs by fighting inflammation. Without it, people are vulnerable to infections or irritants in the air, such as cigarette smoke, and often develop life-threatening lung disease.
“When you give this therapy into the deltoid muscles of the arm, the muscle becomes a factory for making the protein that these individuals are missing,” said Mark L. Brantly, MD, a professor of medicine and molecular genetics and microbiology at UF’s College of Medicine and first author of the study. “The amounts produced were not at therapeutic levels, but the fact we were able to get any produced is an important concept — the proof of principle that it can be done.”
“This study gives us encouraging evidence that gene therapy for Alpha-1 is a realistic possibility,” said John Walsh, president and chief executive officer of the nonprofit Alpha-1 Foundation, which has been supporting research of this kind for more than a decade. “The augmentation therapy available now has slowed down the progression of our lung disease and extended many of our lives. The promise of gene therapy addresses our ongoing issues of convenience, such as weekly infusions, and affordability. The hope of gene therapy is that we may have a one-time, brief series of injections that could allow our own bodies to produce the alpha-1 protein we need to live a normal lifetime.
“The Alpha-1 community is incredibly grateful for the progress that these dedicated investigators have made,” Walsh said.
“What I would tell the alpha-1 community is that this trial does not give us any guarantee, but there is a fighting chance to develop a therapy using this method,” said senior author Terence Flotte, MD, formerly the chairman of pediatrics at UF and now the dean of the School of Medicine, and provost and executive deputy chancellor of UMass Medical School.
The study was funded by grants from the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, UF, the National Center for Research Resources, the Alpha-1 Foundation, and from the study sponsor, Applied Genetic Technologies Corp., or AGTC, a company formed by UF researchers to develop gene therapies. UF holds an equity interest in AGTC. Brantly is the Alpha-1 Foundation endowed research professor at UF and is a consultant for the organization.
