Safety of intradiaphragmatic delivery of adeno-associated virus-mediated alpha-glucosidase (rAAV1-CMV-hGAA) gene therapy in children affected by Pompe disease

Authors

Manuela Corti, University of Florida, United States
Cristina Liberati, University of Florida, United States
Barbara K. Smith, University of Florida, United States
Lee Ann Lawson, University of Florida, United States
Ibrahim S. Tuna, University of Florida, United States
Thomas J. Conlon, University of Florida, United States
Kirsten E. Coleman, University of Florida, United States
Saleem Islam, University of Florida, United StatesFollow
Roland W. Herzog, University of Florida, United States
David D. Fuller, University of Florida, United States

Document Type

Article

Department

Paediatric Surgery

Abstract

A first-in-human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory and neural dysfunction in early-onset Pompe disease was conducted. The primary objective of this study was to assess the safety of rAAV1-CMV-hGAA vector delivered to the diaphragm muscle of Pompe disease subjects with ventilatory insufficiency. Safety was assessed by measurement of change in serum chemistries and hematology, urinalysis, and immune response to GAA and AAV, as well as change in level of health. The data demonstrate that the AAV treatment was safe and there were no adverse events related to the study agent. Adverse events related to the study procedure were observed in subjects with lower baseline neuromuscular function. All adverse events were resolved before the end of the study, except for one severe adverse event determined not to be related to either the study agent or the study procedure. In addition, an anti-capsid and anti-transgene antibody response was observed in all subjects who received rAAV1-CMV-hGAA, except for subjects who received concomitant immunomodulation to manage reaction to enzyme replacement therapy, as per their standard of care. This observation is significant for future gene therapy studies and serves to establish a clinically relevant approach to blocking immune responses to both the AAV capsid protein and transgene product.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Human Gene Therapy Clinical Development

Recommended Citation

Corti, M., Liberati, C., Smith, B. K., Lawson, L. A., Tuna, I. S., Conlon, T. J., Coleman, K. E., Islam, S., Herzog, R. W., Fuller, D. D. (2017). Safety of intradiaphragmatic delivery of adeno-associated virus-mediated alpha-glucosidase (rAAV1-CMV-hGAA) gene therapy in children affected by Pompe disease. Human Gene Therapy Clinical Development, 28(4), 208-218.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_paediatr/96