Long term substrate reduction therapy with ezetimibe alone or associated with statins in three adult patients with lysosomal acid lipase deficiency

Maja Di Rocco, Livia Pisciotta, Annalisa Madeo, Marta Bertamino, Stefano Bertolini

Research output: Contribution to journalArticle

Abstract

Background: Lysosomal acid lipase deficiency is an autosomal recessive metabolic disease with a wide range of severity from Wolman Disease to Cholesterol Ester Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has been approved by drug agencies for treatment of this lysosomal disease. Ezetimibe is an azetidine derivative which blocks Niemann Pick C1-Like 1 Protein; as its consequence, plasmatic concentration of low density lipoproteins and other apoB-containing lipoproteins, that are the substrate of lysosomal acid lipase, are decreased. Furthermore, ezetimibe acts by blocking inflammasome activation which is the cause of liver fibrosis in steatohepatitis and in lysosomal storage diseases. Results: Two patients with Cholesterol Ester Storage Disease were treated with ezetimibe for 9 years and a third patients for 10 years. Treatment was supplemented with low dose of atorvastatin in the first two patients during the last 6 years. All patients showed a significant reduction of alanine aminotransferase, cholesterol and triglyceride. Furthermore, no progression of liver fibrosis was demonstrated. Conclusion: In this observational case series, ezetimibe is effective, safe, and sustainable treatment for lysosomal acid lipase deficiency. Further studies are warranted to demonstrate that ezetimibe is an alternative therapy to enzyme replacement therapy.

Original languageEnglish
Article number24
JournalOrphanet Journal of Rare Diseases
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 27 2018

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cholesterol Ester Storage Disease
Enzyme Replacement Therapy
Liver Cirrhosis
Wolman Disease
Inflammasomes
Lysosomal Storage Diseases
Sterol Esterase
Therapeutics
Metabolic Diseases
Apolipoproteins B
Fatty Liver
Complementary Therapies
Alanine Transaminase
LDL Lipoproteins
Lipoproteins
Triglycerides
Cholesterol
Ezetimibe
Lysosomal acid lipase deficiency

Keywords

  • Ezetimibe
  • Lysosomal acid lipase deficiency
  • Substrate reduction therapy

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

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abstract = "Background: Lysosomal acid lipase deficiency is an autosomal recessive metabolic disease with a wide range of severity from Wolman Disease to Cholesterol Ester Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has been approved by drug agencies for treatment of this lysosomal disease. Ezetimibe is an azetidine derivative which blocks Niemann Pick C1-Like 1 Protein; as its consequence, plasmatic concentration of low density lipoproteins and other apoB-containing lipoproteins, that are the substrate of lysosomal acid lipase, are decreased. Furthermore, ezetimibe acts by blocking inflammasome activation which is the cause of liver fibrosis in steatohepatitis and in lysosomal storage diseases. Results: Two patients with Cholesterol Ester Storage Disease were treated with ezetimibe for 9 years and a third patients for 10 years. Treatment was supplemented with low dose of atorvastatin in the first two patients during the last 6 years. All patients showed a significant reduction of alanine aminotransferase, cholesterol and triglyceride. Furthermore, no progression of liver fibrosis was demonstrated. Conclusion: In this observational case series, ezetimibe is effective, safe, and sustainable treatment for lysosomal acid lipase deficiency. Further studies are warranted to demonstrate that ezetimibe is an alternative therapy to enzyme replacement therapy.",
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T1 - Long term substrate reduction therapy with ezetimibe alone or associated with statins in three adult patients with lysosomal acid lipase deficiency

AU - Di Rocco, Maja

AU - Pisciotta, Livia

AU - Madeo, Annalisa

AU - Bertamino, Marta

AU - Bertolini, Stefano

PY - 2018/1/27

Y1 - 2018/1/27

N2 - Background: Lysosomal acid lipase deficiency is an autosomal recessive metabolic disease with a wide range of severity from Wolman Disease to Cholesterol Ester Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has been approved by drug agencies for treatment of this lysosomal disease. Ezetimibe is an azetidine derivative which blocks Niemann Pick C1-Like 1 Protein; as its consequence, plasmatic concentration of low density lipoproteins and other apoB-containing lipoproteins, that are the substrate of lysosomal acid lipase, are decreased. Furthermore, ezetimibe acts by blocking inflammasome activation which is the cause of liver fibrosis in steatohepatitis and in lysosomal storage diseases. Results: Two patients with Cholesterol Ester Storage Disease were treated with ezetimibe for 9 years and a third patients for 10 years. Treatment was supplemented with low dose of atorvastatin in the first two patients during the last 6 years. All patients showed a significant reduction of alanine aminotransferase, cholesterol and triglyceride. Furthermore, no progression of liver fibrosis was demonstrated. Conclusion: In this observational case series, ezetimibe is effective, safe, and sustainable treatment for lysosomal acid lipase deficiency. Further studies are warranted to demonstrate that ezetimibe is an alternative therapy to enzyme replacement therapy.

AB - Background: Lysosomal acid lipase deficiency is an autosomal recessive metabolic disease with a wide range of severity from Wolman Disease to Cholesterol Ester Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has been approved by drug agencies for treatment of this lysosomal disease. Ezetimibe is an azetidine derivative which blocks Niemann Pick C1-Like 1 Protein; as its consequence, plasmatic concentration of low density lipoproteins and other apoB-containing lipoproteins, that are the substrate of lysosomal acid lipase, are decreased. Furthermore, ezetimibe acts by blocking inflammasome activation which is the cause of liver fibrosis in steatohepatitis and in lysosomal storage diseases. Results: Two patients with Cholesterol Ester Storage Disease were treated with ezetimibe for 9 years and a third patients for 10 years. Treatment was supplemented with low dose of atorvastatin in the first two patients during the last 6 years. All patients showed a significant reduction of alanine aminotransferase, cholesterol and triglyceride. Furthermore, no progression of liver fibrosis was demonstrated. Conclusion: In this observational case series, ezetimibe is effective, safe, and sustainable treatment for lysosomal acid lipase deficiency. Further studies are warranted to demonstrate that ezetimibe is an alternative therapy to enzyme replacement therapy.

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