Eric Wallace, M.D.The University of Alabama at Birmingham is taking part in a groundbreaking Phase I/II clinical trial testing a one‑time, intravenous investigational gene therapy that could transform care for patients with classic Fabry disease.
Fabry disease is a rare, X-linked genetic lysosomal storage disorder caused by a deficient enzyme called alpha-galactosidase A. Without it, a fatty substance called globotriaosylceramide, or GL-3, builds up in cells throughout the body, which can damage the kidneys, heart, nervous system, eyes, gut and skin.
Common symptoms of classic Fabry disease can vary widely but often include burning pain in the hands and feet, particularly during exercise or fever, as well as kidney problems that may progress to kidney failure. Many patients also experience heart complications such as thickening of the heart muscle and irregular heart rhythms, along with an increased risk of stroke.
Additional symptoms may include clusters of small, dark skin lesions called angiokeratomas, gastrointestinal issues like nausea, diarrhea and abdominal pain, and persistent fatigue accompanied by sensitivity to heat and cold.
Classic Fabry disease affects approximately one in 40,000 males. Late-onset Fabry disease may occur as frequently as one in 9,000 people. In women, symptoms are often milder or may go unrecognized — making the disease frequently under-diagnosed.
The current standard of care for Fabry disease is enzyme replacement therapy, which requires biweekly intravenous infusions. The therapy can take hours and can have side effects like infusion-related reactions.
Eric Wallace, M.D., professor of medicine in the Division of Nephrology, serves as principal investigator for the UAB site in the Phase I/II clinical trial of AMT-191, an investigational gene therapy for classic Fabry disease.
In this investigational approach, patients receive a single injection of an engineered, non-replicating viral vector designed to target liver cells. The viral vector delivers the missing alpha-galactosidase gene directly to the liver. The goal is for the liver to begin producing the enzyme on its own, releasing it into the bloodstream to reach cells throughout the body.
“The patient starts making their own enzyme replacement therapy. The hope is that the patient will make enough enzymes to no longer need to go back for an infusion, thus improving their quality of life,” Wallace said. “The fact that the enzyme is constantly made as opposed to only being given every two weeks may improve outcomes.”
UAB has been a national leader in Fabry disease care and research for more than two decades. In 2003, David Warnock, M.D., became the first physician in the country to initiate a patient on commercially available enzyme replacement therapy, and that same patient remains under UAB’s care today.
Most recently, in 2023, Wallace directed the pivotal clinical trial for pegunigalsidase alfa, work that contributed to the therapy’s FDA approval. UAB continues to advance the field through ongoing participation in clinical trials, including studies of substrate reduction therapy, another promising approach for treating Fabry disease.
“The story is not just about gene therapy,” he said. “It is a two-decade-long history of the dedication of UAB to the improvement of the lives of patients with Fabry disease.”