Public Release: 

New enzyme-replacement therapy shows promise for genetic lipid disease treatment

First-of-its-kind therapy, Sebelipase Alfa, has potential to effectively treat Lysosomal Acid Lipase Deficiency

University of Pennsylvania School of Medicine

PHILADELPHIA--Of the more than 50 known lysosomal storage diseases (LSDs)-rare inherited metabolic disorders-only seven can be treated with approved enzyme-replacement therapies. Lysosomal acid lipase deficiency (LALD) is an LSD that causes fatty liver disease and cirrhosis. There is no treatment for the disease, which afflicts 1- 40,000 - 1 in 300,000 people across the world. In this week's New England Journal of Medicine, researchers report results of a trial showing the efficacy of a new enzyme-replacement therapy for LALD. In an accompanying editorial, Daniel J. Rader, MD, chair of the department of Genetics in the Perelman School of Medicine at the University of Pennsylvania, notes that this first-ever hepatocyte-targeting therapy will be pivotal in treating this disease.

In a phase 3 trial in patients with lysosomal acid lipase deficiency, researchers evaluated the safety and effectiveness of the hepatocyte-targeting enzyme-replacement therapy for LALD, known as sebelipase alfa. The therapy works by administering enzymes that specifically target hepatocytes, cells that make up nearly 80 percent of the liver. These enzymes are taken up by the hepatocytes, directed to the lysosomes, and replace the missing lysosomal acid lipase enzymes. With 66 patients involved in the 20-week trial, researchers found that treatment with sebelipase alfa resulted in reduced disease-related liver and blood cholesterol abnormalities, such as cirrhosis, hepatomegaly, and liver fibrosis. More, patients experienced lower cholesterol levels, and reduced liver fat content and size with continued treatment.

"LALD is an underdiagnosed disease with serious medical consequences," Rader said. "Sebelipase alfa could be a game-changer in the treatment of this disease. However, to effectively treat patients, physicians need to think of diagnosing this disorder and initiating this therapy, once available, as early as possible."

Rader also notes that while a larger, longer-term study is needed to prove that this treatment will prevent serious liver consequences, he says "sebelipase alfa has shown great potential for effectively treating and managing this underappreciated genetic lipid disorder."


Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2014, Penn Medicine provided $771 million to benefit our community.

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