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.

A chaperone enhances blood α-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy / Parenti G; Fecarotta S; la Marca G; Rossi B; Ascione S; Donati MA; Morandi LO; Ravaglia S; Pichiecchio A; Ombrone D; Sacchini M; Pasanisi MB; De Filippi P; Danesino C; Della Casa R; Romano A; Mollica C; Rosa M; Agovino T; Nusco E; Porto C; Andria G.. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - STAMPA. - (2014), pp. 2004-2012.

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

LA MARCA, GIANCARLO;OMBRONE, DANIELA;
2014

Abstract

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.
2014
2004
2012
Parenti G; Fecarotta S; la Marca G; Rossi B; Ascione S; Donati MA; Morandi LO; Ravaglia S; Pichiecchio A; Ombrone D; Sacchini M; Pasanisi MB; De Filippi P; Danesino C; Della Casa R; Romano A; Mollica C; Rosa M; Agovino T; Nusco E; Porto C; Andria G.
File in questo prodotto:
File Dimensione Formato  
MTPompe.pdf

Accesso chiuso

Tipologia: Altro
Licenza: Open Access
Dimensione 1.41 MB
Formato Adobe PDF
1.41 MB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/946133
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 66
  • ???jsp.display-item.citation.isi??? 65
social impact