A chaperone enhances blood α-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy

Giancarlo Parenti, Simona Fecarotta, Giancarlo la Marca, Barbara Rossi, Serena Ascione, Maria A lice Donati, Lucia O vidia Morandi, Sabrina Ravaglia, Anna Pichiecchio, Daniela Ombrone, Michele Sacchini, Maria B arbara Pasanisi, Paola De Filippi, Cesare Danesino, Roberto Della Casa, Alfonso Romano, Carmine Mollica, Margherita Rosa, Teresa Agovino, Edoardo NuscoCaterina Porto, Generoso Andria

Research output: Contribution to journalArticlepeer-review


Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone.

Original languageEnglish
Pages (from-to)2004-2012
Number of pages9
JournalMolecular Therapy
Issue number11
Publication statusPublished - Nov 1 2014

ASJC Scopus subject areas

  • Medicine(all)


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