Acid Maltase Deficiency Myopathy Medication

  • Author: Michael Weinik, DO; Chief Editor: Denise I Campagnolo, MD, MS   more...
 
Updated: Jan 18, 2012
 

Medication Summary

Treatment for this fatal disorder is limited.[4, 13] 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. 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.[14] 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, 15]

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.[16] 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.[17]

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Enzyme replacement

Class Summary

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

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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

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.

Coauthor(s)

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.

Specialty Editor Board

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 and American Academy of Physical Medicine and Rehabilitation

Disclosure: Medtronic Neurological None Speaking and teaching

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

Disclosure: Medscape Salary Employment

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 and American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Kelly L Allen, MD  Medical Director, Medevals

Disclosure: Nothing to disclose.

Chief Editor

Denise I Campagnolo, MD, MS  Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers

Denise I Campagnolo, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers

Disclosure: Teva Neuroscience Honoraria Speaking and teaching; Serono-Pfizer Honoraria Speaking and teaching; Genzyme Corporation Grant/research funds investigator; Biogen Idec Grant/research funds investigator; Genentech, Inc Grant/research funds investigator; Eli Lilly & Company Grant/research funds investigator; Novartis investigator; MSDx LLC Grant/research funds investigator; BioMS Technology Corp Grant/research funds investigator; Avanir Pharmaceuticals Grant/research funds investigator

Additional Contributors

The editors would like to thank Daniel A Lee, MD, for his previous association with this article.

References

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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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