Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset Type II Glycogenosis?

Sabrina Ravaglia, Paola De Filippi, Anna Pichiecchio, Michela Ponzio, Kolsoum Saeidi Garaghani, Guy Umberto Poloni, Paola Bini, Cesare Danesino

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The purpose of this study is to analyze the role of genes known to influence muscle performances on the outcome after enzyme replacement treatment (ERT) in type II Glycogenosis (GSDII). We analyzed 16 patients receiving ERT for ≥ two years. We assessed the changes in muscle strength by hand-held dynamometry, muscle mass by quantitative MRI, and resistance to exercise by the 6-minute walking test. Exercise gene assessment included angiotensin converting enzyme insertion/deletion polymorphism (ACE), alpha-actinin3 R577X polymorphism (ACTN3), and peroxisome proliferator activated receptor alpha G/C polymorphism (PPARα). Independent of disease severity, one third of patients had a poor response to ERT, which was found to be associated with ACE DD genotype. The ACTN3 null polymorphism appeared to exert a positive effect on treatment efficacy, while PPARα did not seem to exert any influence at all. We conclude that poor treatment outcome in ACE DD genotypes is in line with previous observation of a worse disease course in this subpopulation, and suggests the need for a more careful follow-up and individualized treatment approaches for these patients. Exercise genes may provide a new opportunity for studying the outcome after treatment and the muscle regeneration abilities in other models of genetic myopathies.

Original languageEnglish
Pages (from-to)104-110
Number of pages7
JournalMolecular Genetics and Metabolism
Volume107
Issue number1-2
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Glycogen Storage Disease Type II
Enzyme Replacement Therapy
Polymorphism
Muscle
Peroxisome Proliferator-Activated Receptors
Genes
Exercise
Muscles
Enzymes
Genotype
PPAR alpha
Genetic Models
Muscle Strength
Peptidyl-Dipeptidase A
Muscular Diseases
Walking
Regeneration
Therapeutics
Hand
Observation

Keywords

  • Enzyme replacement therapy
  • Genetic polymorphisms
  • Glycogen storage disease type II
  • Volumetric MRI

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset Type II Glycogenosis? / Ravaglia, Sabrina; De Filippi, Paola; Pichiecchio, Anna; Ponzio, Michela; Saeidi Garaghani, Kolsoum; Poloni, Guy Umberto; Bini, Paola; Danesino, Cesare.

In: Molecular Genetics and Metabolism, Vol. 107, No. 1-2, 09.2012, p. 104-110.

Research output: Contribution to journalArticle

Ravaglia, Sabrina ; De Filippi, Paola ; Pichiecchio, Anna ; Ponzio, Michela ; Saeidi Garaghani, Kolsoum ; Poloni, Guy Umberto ; Bini, Paola ; Danesino, Cesare. / Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset Type II Glycogenosis?. In: Molecular Genetics and Metabolism. 2012 ; Vol. 107, No. 1-2. pp. 104-110.
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