2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Plasma Lyso-Sphingomyelin, Biomarker for Acid Sphingomyelinase Deficiency: Correlations with Baseline Disease and Response to Olipudase Alfa Treatment in Clinical Trials

Plasma Lyso-Sphingomyelin, Biomarker for Acid Sphingomyelinase Deficiency: Correlations with Baseline Disease and Response to Olipudase Alfa Treatment in Clinical Trials

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This document discusses the use of plasma lyso-sphingomyelin as a biomarker for acid sphingomyelinase deficiency (ASMD) and its correlation with baseline disease and response to olipudase alfa treatment in clinical trials. ASMD is a lysosomal storage disease caused by pathogenic variants in the SMPD1 gene, resulting in the accumulation of sphingomyelin in various organs. The study analyzed data from the ASCEND, ASCEND-Peds, and Phase 1b/LTS trials sponsored by Sanofi.<br /><br />Before treatment with olipudase alfa, plasma lyso-sphingomyelin levels were significantly elevated in all patients in the clinical trials. These levels correlated positively with liver volume and ALT levels in both children and adults, negatively with DLCO and HDL cholesterol, and with spleen volume in adults but not in children. After treatment with olipudase alfa, plasma lyso-sphingomyelin decreased rapidly, but did not normalize, stabilizing after about six months of treatment. The decreases in lyso-sphingomyelin levels paralleled clinical improvements. Missed infusions resulted in marked transient increases in lyso-sphingomyelin.<br /><br />The document also provides information on the statistical analyses conducted and the correlations observed between plasma lyso-sphingomyelin and various clinical variables in both adults and children at baseline. It discusses the characteristics of ASMD and the clinical signs and symptoms associated with the disease.<br /><br />The data support the use of plasma lyso-sphingomyelin as a diagnostic and prognostic biomarker for ASMD in children and adults. The document includes charts and figures showcasing the correlations between lyso-sphingomyelin and other clinical variables, as well as the response to olipudase alfa treatment.<br /><br />In conclusion, plasma lyso-sphingomyelin levels can be used as a biomarker to assess disease severity and response to treatment in patients with ASMD. The data presented in this document provide valuable insights into the use of this biomarker and its correlations with various clinical parameters.

Asset Subtitle

Presenting Author - Melissa Wasserstein, MD; Co-Author - Roberto Giugliani, MD, PhD; Co-Author - Simon A. Jones, MBChB, MRCPCH; Co-Author - Robin Lachmann, MD PhD; Co-Author - Maurizio Scarpa, MD, PhD; Co-Author - Monica Kumar, MD, MPH; Co-Author - Nicole Armstrong, PhD; Co-Author - Mario Aguiar, MD;

Meta Tag

Enzyme Replacement Therapy

Lysosomal Diseases

Metabolic Disorder

Therapy

Co-Author Roberto Giugliani, MD, PhD

Co-Author Simon A. Jones, MBChB, MRCPCH

Co-Author Robin Lachmann, MD PhD

Co-Author Maurizio Scarpa, MD, PhD

Co-Author Monica Kumar, MD, MPH

Co-Author Nicole Armstrong, PhD

Co-Author Mario Aguiar, MD

Presenting Author Melissa Wasserstein, MD

Keywords

plasma lyso-sphingomyelin

biomarker

acid sphingomyelinase deficiency

ASMD

SMPD1 gene

lysosomal storage disease

olipudase alfa treatment

clinical trials

diagnostic biomarker

prognostic biomarker