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Novel treatment options for lysosomal acid lipase deficiency: critical appraisal of sebelipase alfa

Authors Su K, Donaldson E, Sharma R

Received 9 January 2016

Accepted for publication 10 May 2016

Published 17 October 2016 Volume 2016:9 Pages 157—167


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer

Kim Su,1 Emma Donaldson,1 Reena Sharma2

1Division of Gastroenterology/Hepatology, 2The Mark Holland Metabolic Unit, Salford Royal Hospital NHS Foundation Trust, Salford, UK

Lysosomal acid lipase deficiency (LAL-D) is a rare disorder of cholesterol metabolism with an autosomal recessive mode of inheritance. The absence or deficiency of the LAL enzyme gives rise to pathological accumulation of cholesterol esters in various tissues. A severe LAL-D phenotype manifesting in infancy is associated with adrenal calcification and liver and gastrointestinal involvement with characteristic early mortality. LAL-D presenting in childhood and adulthood is associated with hepatomegaly, liver fibrosis, cirrhosis, and premature atherosclerosis. There are currently no curative pharmacological treatments for this life-threatening condition. Supportive management with lipid-modifying agents does not ameliorate disease progression. Hematopoietic stem cell transplantation as a curative measure in infantile disease has mixed success and is associated with inherent risks and complications. Sebelipase alfa (Kanuma) is a recombinant human LAL protein and the first enzyme replacement therapy for the treatment of LAL-D. Clinical trials have been undertaken in infants with rapidly progressive LAL-D and in children and adults with later-onset LAL-D. Initial data have shown significant survival benefits in the infant group and improvements in biochemical parameters in the latter. Sebelipase alfa has received marketing authorization in the United States and Europe as long-term therapy for all affected individuals. The availability of enzyme replacement therapy for this rare and progressive disorder warrants greater recognition and awareness by physicians.

Keywords: sebelipase alfa, LAL deficiency, Wolman disease

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