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Acid Maltase Deficiency Myopathy Medication

  • Author: Stephen Kishner, MD, MHA; Chief Editor: Stephen Kishner, MD, MHA  more...
 
Updated: Apr 28, 2016
 

Medication Summary

Treatment for this fatal disorder is limited.[4, 16] A copious amount of research into acid maltase deficiency (AMD) is exploring the possibility of replacing the deficient enzyme by means of gene therapy.[5] Up to this point, the results have been frustratingly unfruitful. Future strategies may include in-vivo or ex-vivo gene therapy and/or mesenchymal stem cell or bone marrow transplantation approaches. Some results have been positive in animal models, but to extrapolate these results to the human form, new approaches to AMD must be determined and improvements in the access to cardiac and skeletal muscle must be made. Newer, more efficacious and innocuous vectors also must be discovered. L-alanine supplementation in late-onset AMD has been shown to decrease resting energy expenditure.

Emerging research has shown that infusions of recombinant human alpha-glucosidase from rabbit milk is helpful for stabilizing pulmonary function and improving muscle fatigue in early onset and late-onset Pompe disease.[17, 18] The younger and least affected children have shown the most improvement and delay in the progression of the disease process.

Originally described in the treatment of mice with glycogen storage disease, Ven den Hout et al, in an open-label study, treated 4 babies with recombinant human alpha-glucosidase obtained from rabbit milk.[19] Recombinant glucosidase was administered intravenously at a weekly dose of 15-20 mg/kg and later was increased to 40 mg/kg. Alpha-glucosidase activity normalized in muscle, the tissue morphology and motor and cardiac function improved, and the left ventricular mass index significantly decreased. Normal neurologic development was noted in all patients. Subsequent studies have involved the use of recombinant human alpha-glucosidase derived from Chinese hamster ovary cells.[2, 20]

In a 2009 open-label, multicenter study, Nicolino et al employed intravenous treatment with recombinant human alpha-glucosidase in 21 patients, aged 3-43 months, with advanced Pompe disease.[17] The drug was administered every 2 weeks for up to 168 weeks; the investigators found that, compared with an untreated reference cohort, the risk of death in the treated children was reduced by 79% (P < 0.001), and the risk that invasive ventilation would be required was decreased by 58% (P = 0.02).

The lessons learned from research into AMD may lead to better understanding and treatment of other genetic disorders.[21]

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Enzyme replacement

Class Summary

Used as replacement therapy. Recombinant human enzyme alpha-glucosidase has recently been designated an orphan drug.[22]

Previously, although the form of alglucosidase alfa known as Myozyme had been approved by the US Food and Drug Administration (FDA) for use in the treatment of patients younger than 8 years with infantile acid maltase deficiency (Pompe disease), the form known as Lumizyme had been approved only for patients with late-onset acid maltase deficiency who were aged 8 years or older. In 2014, however, the FDA also approved Lumizyme for patients younger than 8 years.[23]

Alglucosidase alfa (Myozyme)

 

Recombinant human enzyme alpha-glucosidase (rhGAA) indicated as an orphan drug for treatment of Pompe disease. Replaces rhGAA, which is deficient or lacking in persons with Pompe disease. Alpha-glucosidase is essential for normal muscle development and function. Binds to mannose-6-phosphate receptors and then is transported into lysosomes; undergoes proteolytic cleavage that results in increased enzymatic activity and ability to cleave glycogen. Improves infant survival without requiring invasive ventilatory support compared with historical controls without treatment.

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Contributor Information and Disclosures
Author

Stephen Kishner, MD, MHA Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans

Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Eric F Sterne, MD Resident Physician, Department of Physical Medicine and Rehabilitation, Louisiana State University School of Medicine in New Orleans

Eric F Sterne, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kat Kolaski, MD Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine

Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kishner, MD, MHA Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans

Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Elizabeth A Moberg-Wolff, MD Medical Director, Pediatric Rehabilitation Medicine Associates

Elizabeth A Moberg-Wolff, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Acknowledgements

Frank J King, MD Clinical Instructor, Department of Physical Medicine and Rehabilitation, Georgia Pain Physicians/Emory School of Medicine

Frank J King, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, and Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Daniel A Lee, MD Intern, Department of Family Medicine, Contra Costa Regional Medical Center

Disclosure: Nothing to disclose.

Michael Weinik, DO Associate Chairman, Associate Professor, Physical Medicine and Rehabilitation, Temple University Hospital

Michael Weinik, DO is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

References
  1. Fukuda T, Roberts A, Plotz PH, et al. Acid alpha-glucosidase deficiency (Pompe disease). Curr Neurol Neurosci Rep. 2007 Jan. 7(1):71-7. [Medline].

  2. van der Ploeg AT, Reuser AJ. Pompe's disease. Lancet. 2008 Oct 11. 372(9646):1342-53. [Medline].

  3. Bembi B, Cerini E, Danesino C, et al. Management and treatment of glycogenosis type II. Neurology. 2008 Dec 2. 71(23 Suppl 2):S12-36. [Medline].

  4. Richard E, Douillard-Guilloux G, Caillaud C. New insights into therapeutic options for Pompe disease. IUBMB Life. 2011 Nov. 63(11):979-86. [Medline].

  5. Byrne BJ, Falk DJ, Pacak CA, Nayak S, Herzog RW, Elder ME, et al. Pompe disease gene therapy. Hum Mol Genet. 2011 Apr 15. 20:R61-8. [Medline]. [Full Text].

  6. Manganelli F, Ruggiero L. Clinical features of Pompe disease. Acta Myol. 2013 Oct. 32(2):82-4. [Medline]. [Full Text].

  7. Hagemans ML, Winkel LP, Van Doorn PA, et al. Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. Brain. 2005 Mar. 128(Pt 3):671-7. [Medline]. [Full Text].

  8. Hagemans ML, Winkel LP, Hop WC, et al. Disease severity in children and adults with Pompe disease related to age and disease duration. Neurology. 2005 Jun 28. 64(12):2139-41. [Medline].

  9. Hagemans ML, Hop WJ, Van Doorn PA, et al. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology. 2006 Feb 28. 66(4):581-3. [Medline].

  10. Muller-Felber W, Horvath R, Gempel K, et al. Late onset Pompe disease: clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patients. Neuromuscul Disord. 2007 Oct. 17(9-10):698-706. [Medline].

  11. Van der Beek NA, Hagemans ML, Reuser AJ, et al. Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease. Neuromuscul Disord. 2009 Feb. 19(2):113-7. [Medline].

  12. Papadimas GK, Spengos K, Papadopoulos C, Manta P. Late Onset Glycogen Storage Disease Type II: Pitfalls in the Diagnosis. Eur Neurol. 2011 Dec 15. 67(2):65-68. [Medline].

  13. Vissing J, Lukacs Z, Straub V. Diagnosis of Pompe disease: muscle biopsy vs blood-based assays. JAMA Neurol. 2013 Jul. 70(7):923-7. [Medline].

  14. Bembi B, Cerini E, Danesino C, et al. Diagnosis of glycogenosis type II. Neurology. 2008 Dec 2. 71(23 Suppl 2):S4-11. [Medline].

  15. Jones HN, Crisp KD, Robey RR, Case LE, Kravitz RM, Kishnani PS. Respiratory muscle training (RMT) in late-onset Pompe disease (LOPD): effects of training and detraining. Mol Genet Metab. 2016 Feb. 117 (2):120-8. [Medline].

  16. Parenti G, Andria G. Pompe disease: from new views on pathophysiology to innovative therapeutic strategies. Curr Pharm Biotechnol. 2011 Jun. 12(6):902-15. [Medline].

  17. Nicolino M, Byrne B, Wraith JE, et al. Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med. 2009 Mar. 11(3):210-219. [Medline].

  18. Anderson LJ, Henley W, Wyatt KM, et al. Effectiveness of enzyme replacement therapy in adults with late-onset Pompe disease: results from the NCS-LSD cohort study. J Inherit Metab Dis. 2014 Jun 7. [Medline].

  19. Van den Hout H, Reuser AJ, Vulto AG, et al. Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet. 2000 Jul 29. 356(9227):397-8. [Medline].

  20. Rossi M, Parenti G, Della Casa R, et al. Long-term enzyme replacement therapy for Pompe disease with recombinant human alpha-glucosidase derived from Chinese hamster ovary cells. J Child Neurol. 2007 May. 22(5):565-73. [Medline].

  21. Schoser B, Hill V, Raben N. Therapeutic approaches in glycogen storage disease type II/Pompe Disease. Neurotherapeutics. 2008 Oct. 5(4):569-78. [Medline]. [Full Text].

  22. Güngör D, de Vries JM, Brusse E, Kruijshaar ME, Hop WC, Murawska M, et al. Enzyme replacement therapy and fatigue in adults with Pompe disease. Mol Genet Metab. 2013 Jun. 109(2):174-8. [Medline].

  23. FDA. FDA expands approval of drug to treat Pompe disease to patients of all ages; removes risk mitigation strategy requirements. US Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm407563.htm. Accessed: Apr 28, 2016.

  24. van der Ploeg AT. Monitoring of pulmonary function in Pompe disease: a muscle disease with new therapeutic perspectives. Eur Respir J. 2005 Dec. 26(6):984-5.

  25. Winkel LP, Kamphoven JH, van den Hout HJ, et al. Morphological changes in muscle tissue of patients with infantile Pompe''s disease receiving enzyme replacement therapy. Muscle Nerve. 2003 Jun. 27(6):743-51. [Medline].

  26. Winkel LP, Van den Hout JM, Kamphoven JH, et al. Enzyme replacement therapy in late-onset Pompe's disease: a three-year follow-up. Ann Neurol. 2004 Apr. 55(4):495-502.

 
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Glycogen molecule; by cleaving glycogen's 1,4 and 1,6 alpha-glycosidic linkages, the enzyme acid maltase gives rise to free glucose molecules.
Metabolic pathways of carbohydrates.
 
 
 
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