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. 1998 Feb 15;101(4):827–833. doi: 10.1172/JCI1722

Clinical and metabolic correction of pompe disease by enzyme therapy in acid maltase-deficient quail.

T Kikuchi 1, H W Yang 1, M Pennybacker 1, N Ichihara 1, M Mizutani 1, J L Van Hove 1, Y T Chen 1
PMCID: PMC508631  PMID: 9466978

Abstract

Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase (GAA), a glycogen degrading lysosomal enzyme. GAA-deficient (AMD) Japanese quails exhibit progressive myopathy and cannot lift their wings, fly, or right themselves from the supine position (flip test). Six 4-wk-old acid maltase-deficient quails, with the clinical symptoms listed, were intravenously injected with 14 or 4.2 mg/kg of precursor form of recombinant human GAA or buffer alone every 2-3 d for 18 d (seven injections). On day 18, both high dose-treated birds (14 mg/kg) scored positive flip tests and flapped their wings, and one bird flew up more than 100 cm. GAA activity increased in most of the tissues examined. In heart and liver, glycogen levels dropped to normal and histopathology was normal. In pectoralis muscle, morphology was essentially normal, except for increased glycogen granules. In sharp contrast, sham-treated quail muscle had markedly increased glycogen granules, multi-vesicular autophagosomes, and inter- and intrafascicular fatty infiltrations. Low dose-treated birds (4.2 mg/kg) improved less biochemically and histopathologically than high dose birds, indicating a dose-dependent response. Additional experiment with intermediate doses and extended treatment (four birds, 5.7-9 mg/kg for 45 d) halted the progression of the disease. Our data is the first to show that an exogenous protein can target to muscle and produce muscle improvement. These data also suggest enzyme replacement with recombinant human GAA is a promising therapy for human Pompe disease.

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Selected References

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  1. Barton N. W., Furbish F. S., Murray G. J., Garfield M., Brady R. O. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1913–1916. doi: 10.1073/pnas.87.5.1913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  3. Canfield W. M., Kornfeld S. The chicken liver cation-independent mannose 6-phosphate receptor lacks the high affinity binding site for insulin-like growth factor II. J Biol Chem. 1989 May 5;264(13):7100–7103. [PubMed] [Google Scholar]
  4. Crawley A. C., Niedzielski K. H., Isaac E. L., Davey R. C., Byers S., Hopwood J. J. Enzyme replacement therapy from birth in a feline model of mucopolysaccharidosis type VI. J Clin Invest. 1997 Feb 15;99(4):651–662. doi: 10.1172/JCI119208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fujita T., Nonaka I., Sugita H. Japanese quail and human acid maltase deficiency: a comparative study. Brain Dev. 1991 Jul;13(4):247–255. doi: 10.1016/s0387-7604(12)80058-1. [DOI] [PubMed] [Google Scholar]
  6. Fuller M., Van der Ploeg A., Reuser A. J., Anson D. S., Hopwood J. J. Isolation and characterisation of a recombinant, precursor form of lysosomal acid alpha-glucosidase. Eur J Biochem. 1995 Dec 15;234(3):903–909. doi: 10.1111/j.1432-1033.1995.903_a.x. [DOI] [PubMed] [Google Scholar]
  7. Funk B., Kessler U., Eisenmenger W., Hansmann A., Kolb H. J., Kiess W. Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy. J Clin Endocrinol Metab. 1992 Aug;75(2):424–431. doi: 10.1210/jcem.75.2.1379254. [DOI] [PubMed] [Google Scholar]
  8. Harris R. E., Hannon D., Vogler C., Hug G. Bone marrow transplantation in type IIa glycogen storage disease. Birth Defects Orig Artic Ser. 1986;22(1):119–132. [PubMed] [Google Scholar]
  9. Hershfield M. S., Buckley R. H., Greenberg M. L., Melton A. L., Schiff R., Hatem C., Kurtzberg J., Markert M. L., Kobayashi R. H., Kobayashi A. L. Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med. 1987 Mar 5;316(10):589–596. doi: 10.1056/NEJM198703053161005. [DOI] [PubMed] [Google Scholar]
  10. Higuchi I., Nonaka I., Usuki F., Ishiura S., Sugita H. Acid maltase deficiency in the Japanese quail; early morphological event in skeletal muscle. Acta Neuropathol. 1987;73(1):32–37. doi: 10.1007/BF00695499. [DOI] [PubMed] [Google Scholar]
  11. Howell J. M., Dorling P. R., Cook R. D., Robinson W. F., Bradley S., Gawthorne J. M. Infantile and late onset form of generalised glycogenosis type II in cattle. J Pathol. 1981 Aug;134(4):267–277. doi: 10.1002/path.1711340403. [DOI] [PubMed] [Google Scholar]
  12. Kakkis E. D., McEntee M. F., Schmidtchen A., Neufeld E. F., Ward D. A., Gompf R. E., Kania S., Bedolla C., Chien S. L., Shull R. M. Long-term and high-dose trials of enzyme replacement therapy in the canine model of mucopolysaccharidosis I. Biochem Mol Med. 1996 Aug;58(2):156–167. doi: 10.1006/bmme.1996.0044. [DOI] [PubMed] [Google Scholar]
  13. Kornfeld S. Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu Rev Biochem. 1992;61:307–330. doi: 10.1146/annurev.bi.61.070192.001515. [DOI] [PubMed] [Google Scholar]
  14. Lauer R. M., Mascarinas T., Racela A. S., Diehl A. M., Brown B. I. Administration of a mixture of fungal glucosidases to a patient with type II glycogenosis (Pompe's disease). Pediatrics. 1968 Oct;42(4):672–676. [PubMed] [Google Scholar]
  15. Murakami H., Takagi A., Nanaka S., Ishiura S., Sugita H. [Glycogenosis II in Japanese quails]. Jikken Dobutsu. 1980 Oct;29(4):475–478. [PubMed] [Google Scholar]
  16. O'Sullivan B. M., Healy P. J., Fraser I. R., Nieper R. E., Whittle R. J., Sewell C. A. Generalised glycogenosis in Brahman cattle. Aust Vet J. 1981 May;57(5):227–229. doi: 10.1111/j.1751-0813.1981.tb02666.x. [DOI] [PubMed] [Google Scholar]
  17. Reuser A. J., Koster J. F., Hoogeveen A., Galjaard H. Biochemical, immunological, and cell genetic studies in glycogenosis type II. Am J Hum Genet. 1978 Mar;30(2):132–143. [PMC free article] [PubMed] [Google Scholar]
  18. Usuki F., Ishiura S., Sugita H. Developmental study of alpha-glucosidases in Japanese quails with acid maltase deficiency. Muscle Nerve. 1986 Jul-Aug;9(6):537–543. doi: 10.1002/mus.880090610. [DOI] [PubMed] [Google Scholar]
  19. Van Hove J. L., Yang H. W., Wu J. Y., Brady R. O., Chen Y. T. High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):65–70. doi: 10.1073/pnas.93.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vogler C., Sands M., Higgins A., Levy B., Grubb J., Birkenmeier E. H., Sly W. S. Enzyme replacement with recombinant beta-glucuronidase in the newborn mucopolysaccharidosis type VII mouse. Pediatr Res. 1993 Dec;34(6):837–840. doi: 10.1203/00006450-199312000-00028. [DOI] [PubMed] [Google Scholar]
  21. Watson J. G., Gardner-Medwin D., Goldfinch M. E., Pearson A. D. Bone marrow transplantation for glycogen storage disease type II (Pompé's disease) N Engl J Med. 1986 Feb 6;314(6):385–385. doi: 10.1056/nejm198602063140611. [DOI] [PubMed] [Google Scholar]
  22. Wenk J., Hille A., von Figura K. Quantitation of Mr 46000 and Mr 300000 mannose 6-phosphate receptors in human cells and tissues. Biochem Int. 1991 Mar;23(4):723–731. [PubMed] [Google Scholar]
  23. Wewers M. D., Casolaro M. A., Sellers S. E., Swayze S. C., McPhaul K. M., Wittes J. T., Crystal R. G. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med. 1987 Apr 23;316(17):1055–1062. doi: 10.1056/NEJM198704233161704. [DOI] [PubMed] [Google Scholar]
  24. Williams J. C., Murray A. K. Enzyme replacement in Pompe disease with an alpha-glucosidase-low density lipoprotein complex. Birth Defects Orig Artic Ser. 1980;16(1):415–423. [PubMed] [Google Scholar]
  25. Yang Y. W., Robbins A. R., Nissley S. P., Rechler M. M. The chick embryo fibroblast cation-independent mannose 6-phosphate receptor is functional and immunologically related to the mammalian insulin-like growth factor-II (IGF-II)/man 6-P receptor but does not bind IGF-II. Endocrinology. 1991 Feb;128(2):1177–1189. doi: 10.1210/endo-128-2-1177. [DOI] [PubMed] [Google Scholar]
  26. de Barsy T., Jacquemin P., Van Hoof F., Hers H. G. Enzyme replacement in Pompe disease: an attempt with purified human acid alpha-glucosidase. Birth Defects Orig Artic Ser. 1973 Mar;9(2):184–190. [PubMed] [Google Scholar]

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