Biomarker analysis of Morquio syndrome: identification of disease state and drug responsive markers

Orphanet J Rare Dis. 2011 Dec 16:6:84. doi: 10.1186/1750-1172-6-84.

Abstract

Background: This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis (MPS) IVA.

Methods: Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy controls and 78 MPSIVA patients not receiving ERT to test for significant correlations to the presence of MPSIVA. MPSIVA samples were also tested for correlations between candidate biomarkers and age, endurance, or urinary keratin sulfate (KS) levels. Then, levels of the same 88 analytes were followed over 36 weeks in 20 MPSIVA patients receiving ERT to test for significant correlations related to ERT, age, or endurance.

Results: Nineteen candidate biomarkers were significantly different between MPSIVA and unaffected individuals. Of these, five also changed significantly in response to ERT: alpha-1-antitrypsin, eotaxin, lipoprotein(a), matrix metalloprotein (MMP)-2, and serum amyloid P. Three of these were significantly lower in MPSIVA individuals versus unaffected controls and were increased during ERT: alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P.

Conclusions: Candidate biomarkers alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPSIVA patients.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Biomarkers / urine*
  • Chondroitinsulfatases / administration & dosage*
  • Chondroitinsulfatases / therapeutic use
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Enzyme Replacement Therapy / adverse effects
  • Enzyme Replacement Therapy / methods*
  • Female
  • Humans
  • Keratins / urine
  • Lipoprotein(a) / blood
  • Male
  • Middle Aged
  • Mucopolysaccharidoses / physiopathology
  • Mucopolysaccharidoses / therapy*
  • Mucopolysaccharidosis IV / physiopathology*
  • Mucopolysaccharidosis IV / therapy*
  • Serum Amyloid P-Component / metabolism
  • Treatment Outcome
  • Young Adult
  • alpha 1-Antitrypsin / blood

Substances

  • Biomarkers
  • Lipoprotein(a)
  • SERPINA1 protein, human
  • Serum Amyloid P-Component
  • alpha 1-Antitrypsin
  • Keratins
  • Chondroitinsulfatases
  • GALNS protein, human