Pompe disease is a rare, autosomal recessive disease that affects between 1 in 40,000 and 1 in 300,000 live births.1 This disease is also referred to as glycogen storage disease (GSD) type II or acid maltase deficiency. Many therapies are used to slow the progression of the disease, including enzyme replacement therapy (ERT), experimental gene therapy, pulmonary rehabilitation therapy, physical therapy, and speech language therapy.
Enzyme Replacement Therapy
Alpha-glucosidase (GAA) is a critical enzyme that impacts normal muscle development and function. GAA binds to mannose-6-phosphate receptors for transport into the lysosomes where it is cleaved to increase its enzymatic activity and ability to break down glucose.2
The recombinant human enzyme alpha-glucosidase (rhGAA) recently obtained Orphan Drug classification.2 Enzyme replacement therapy uses repeated intravenous infusions of rhGAA to treat Pompe disease by replacing low levels of GAA in patients of all age groups.2,3 In infants with Pompe disease, rhGAA increases infant survival rate and reduces the need for ventilatory assistance.2 One study indicated the safety and efficacy of higher doses of rhGAA (40 mg/kg weekly instead of the standard 20 mg/kg every other week), leading to improved gross motor outcomes, lingual strength, pulmonary function tests, and biochemical markers in early-onset Pompe disease.4
The first 2 US Food and Drug Administration (FDA)-approved rhGAA ERTs for Pompe disease are Lumizyme® (alglucosidase alfa) and Myozyme® (alglucosidase alfa, recombinant human GAA). Myozyme is indicated for infantile-onset Pompe disease, while Lumizyme is indicated for patients ≥ 8 years of age. Both have improved patient survival rates.1
While it is still in development, in vivo gene therapy uses GAA gene transfer with adeno-associated virus (AAV) vectors to aid in stable production of the GAA enzyme to treat Pompe disease. Gene therapy has been shown to reduce lysosomal glycogen storage and improve phenotypic characteristics of Pompe disease in preclinical studies. Emerging clinical trial data evaluating gene therapy treatment of other diseases with protein deficiencies indicate that gene therapy may be a potentially safe and efficacious treatment for Pompe disease.3
Pulmonary Rehabilitation Therapy
Pulmonary rehabilitation therapy strengthens the respiratory muscles to reduce or delay the need for mechanical ventilation in adults with late-onset Pompe disease (LOPD).5 One study showed that inspiratory muscle training (IMT) used in conjunction with ERT to treat patients with LOPD showed a positive effect on maximum inspiratory pressure.6 Another study indicated that a combination of AAV gene therapy and respiratory exercise training improved diaphragmatic motor function.7
Physical therapy counters the hypotonicity and skeletal muscle decline found in Pompe disease by developing individualized exercise programs including aerobic conditioning, resistance training, and core stabilization. These tailored exercise programs assist in building muscle tone, strengthening functional muscle contractility, increasing oxygen uptake capacity, improving endurance and body composition, and slowing deterioration of skeletal muscle. Investigators in a study measuring the feasibility and effects of such exercise training on individuals with Pompe disease reported significant increases in muscular endurance, duration of hold in core stability exercises, maximum work capacity, maximum ventilatory threshold (VT), and proximal muscle strength.8
Speech Language Therapy
Facial-muscle weakness, speech disorders, and progressive dysphagia are common in long-term survivors receiving ERT for classic infantile Pompe disease.9 These disease symptoms require assessment by a certified speech language pathologist who can provide specific exercises to strengthen the facial and swallowing muscles or recommend certain diet modifications such as using thickening agents in thin liquids and chopping food into much smaller pieces. Speech language therapy has the potential to improve the ease of swallowing, prevent aspiration, improve speech, and increase caloric intake in individuals with Pompe disease.9,10
- Guo J, Kelton CML, Guo JJ. Recent developments, utilization, and spending trends for Pompe disease therapies. Am Health Drug Benefits. 2012;5(3):182-189.
- Defendi GL. Genetics of glycogen-storage disease type II (Pompe disease) medication: enzyme replacement. Medscape. Updated February 29, 2016. Accessed July 20, 2021.
- Colella P, Mingozzi F. Gene therapy for Pompe disease: the time is now. Hum Gene Ther. 2019;30(10):1245-1262. doi:10.1089/hum.2019.109
- Khan AA, Case LE, Herbert M, et al. Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: a clinical study and review of the literature. Genet Med. 2020;22(5):898-907. doi:10.1038/s41436-019-0738-0
- Fernández CG, Rosso RE. Role of respiratory rehabilitation in Pompe disease: a case report. J Neuromuscul Dis. 2015;2(s1):S16-S17. doi:10.3233/JND-159016
- Aslan GK, Huseyinsinoglu BE, Oflazer P, Gurses N, Kiyan E. Inspiratory muscle training in late-onset Pompe disease: the effects on pulmonary function tests, quality of life, and sleep quality. Lung. 2016;194(4):555-561. doi:10.1007/s00408-016-9881-4
- Smith BK, Martin AD, Lawson LA, et al. Inspiratory muscle conditioning exercise and diaphragm gene therapy in Pompe disease: clinical evidence of respiratory plasticity. Exp Neurol. 2017;287(Pt 2):216-224. doi:10.1016/j.expneurol.2016.07.013
- van den Berg LEM, Favejee MM, Wens SCA, et al. Safety and efficacy of exercise training in adults with Pompe disease: evaluation of endurance, muscle strength and core stability before and after a 12 week training program. Orphanet J Rare Dis. 2015;10:87. doi:10.1186/s13023-015-0303-0
- van Gelder CM, van Capelle CI, Ebbink BJ, et al. Facial-muscle weakness, speech disorders and dysphagia are common in patients with classic infantile Pompe disease treated with enzyme therapy. J Inherit Metab Dis. 2012;35(3):505-511. doi:10.1007/s10545-011-9404-7
- Pompe disease and diet. Pompe Disease News. Accessed July 20, 2021.
Reviewed by Debjyoti Talukdar, MD, on 7/27/2021.
Reviewed by Debjyoti Talukdar, MD, on 7/27/2021.