Emanuela Lacaná, Ph.D., a team leader in the Division of Therapeutic Protein, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration in Bethesda, MD. Her scientific interests focus on the review and advancement of product quality for biotechnology-based rare disease drugs.
Version of Record online: 17 JAN 2012
Published 2012 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Advancements in Pompe Disease
Volume 160C, Issue 1, pages 30–39, 15 February 2012
How to Cite
Lacaná, E., Yao, L. P., Pariser, A. R. and Rosenberg, A. S. (2012), The role of immune tolerance induction in restoration of the efficacy of ERT in Pompe disease. Am. J. Med. Genet., 160C: 30–39. doi: 10.1002/ajmg.c.31316
Emanuela Lacaná and Lynne P. Yao contributed equally to this study.
The views expressed in this article represent the opinions of the authors and do not necessarily represent the policy of the US Food and Drug Administration.
The authors have indicated they have no financial relationships relevant to this article to disclose.
How to cite this article: Lacaná E, Yao LP, Pariser AR, Rosenberg AS. 2012. The role of immune tolerance induction in restoration of the efficacy of ERT in Pompe disease. Am J Med Genet Part C Semin Med Genet 160C:30–39.
- Issue online: 23 JAN 2012
- Version of Record online: 17 JAN 2012
- Pompe disease;
- glycogen storage disease type II;
- lysosomal storage diseases;
- enzyme replacement therapy;
- cross-reactive immunologic material;
Pompe disease is a lysosomal storage disorder caused by deficiency in the enzyme acid α-glucosidase (GAA). Pompe disease is characterized by the accumulation of glycogen, predominantly in muscle tissue, leading to progressive muscle weakness, loss of motor, respiratory, and, in the infantile-onset form, cardiac function. Disease progression is highly variable depending on phenotype, but premature death due to respiratory complications occurs in most patients. Beginning in 2006, approved alglucosidase alfa enzyme replacement therapies [recombinant human (rh) GAA] have been available to treat Pompe patients. Treatment of classic infantile-onset patients, who manifest the severest form of the disease, with alglucosidase alfa (Myozyme®) has led to extended survival and an evolving understanding of the pathophysiology and course of the disease. Moreover, such treatment has brought to light the role of the immune response in abrogating the efficacy of rhGAA in classic infantile-onset patients with severe genetic mutations. Thus, optimization of treatment for such patients includes development and utilization of strategies to prevent or eliminate immune responses, including modulating the immune system (prophylactic and therapeutic immune tolerance induction regimens) and engineering the enzyme to be less immunogenic and more effective. Future research is also critical for evaluating and mitigating novel disease-associated pathologies uncovered by prolonged survival of infantile-onset patients including development of novel therapeutics, and for protein design strategies to increase delivery of enzyme replacement therapy to critical target tissues. Such efforts would be greatly bolstered by further development of predictive animal models and biomarkers to facilitate clinical trials and patient management. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.