Albuterol as an adjunctive treatment to enzyme replacement therapy in infantile-onset Pompe disease

Yin-Hsiu Chien; Wuh-Liang Hwu; Ni-Chung Lee; Fuu-Jen Tsai; Dwight D Koeberl; Wen-Hui Tsai; Pao-Chin Chiu; Chaw-Liang Chang

doi:10.1016/j.ymgmr.2017.04.004

Albuterol as an adjunctive treatment to enzyme replacement therapy in infantile-onset Pompe disease

Mol Genet Metab Rep. 2017 Apr 25:11:31-35. doi: 10.1016/j.ymgmr.2017.04.004. eCollection 2017 Jun.

Authors

Yin-Hsiu Chien^{1

2

3}, Wuh-Liang Hwu^{1

2

3}, Ni-Chung Lee^{1

2

3}, Fuu-Jen Tsai⁴, Dwight D Koeberl⁵, Wen-Hui Tsai⁶, Pao-Chin Chiu⁷, Chaw-Liang Chang⁸

Affiliations

¹ Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
² Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
³ Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan.
⁴ Department of Pediatrics, College of Chinese Medicine, Taichung, Taiwan.
⁵ Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
⁶ Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan.
⁷ Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
⁸ Department of Pediatrics, Cathay General Hospital, Hsinchu, Taiwan.

Abstract

Background: Early initiation of enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase is an effective treatment for patients with infantile-onset Pompe disease (IOPD) but cannot prevent a slow progression of myopathy. Albuterol has been shown to be helpful in adult patients with Pompe disease, and therefore, we administered an open-label adjunctive therapy with albuterol in IOPD patients undergoing ERT.

Methods: Fourteen patients, aged 2 to 12 years, were enrolled in this study; all of them had a disease onset before 12 months of life, and 13 of them were ambulatory because of early initiation of ERT. All patients received albuterol (also referred to as salbutamol) 12 mg daily for 26 weeks. The outcome measurements included a 6-minute walk test, four-stair climb test (SCT), the standing/walking/running/jumping domains of Gross Motor Function Measure-88, speech quality, serum creatine kinase, and urinary glucose tetrasaccharide. Outcome and safety measurements were evaluated at baseline, and at 1, 3, and 6 months (26 weeks) after entering the trial.

Results: After a period of 26 weeks, among the 12 patients who were able to complete the SCT, the median time needed decreased by 22% (p = 0.034). Other parameters inconsistently improved in a variety of individuals. Eleven adverse events, including nausea, urinary frequency, and tachycardia, were potentially related to the study drug, but all were mild and disappeared after a brief drug withdrawal. One patient was actively withdrawn from the trial because of poor compliance.

Conclusions: The results of our study suggest that albuterol showed a good safety profile as an adjunctive treatment in our IOPD cohort, although the benefits are limited.

Keywords: 4-Stair climb test; 6-Min walk test; 6MWT, 6-minute walk test; AE, adverse event; Albuterol; CI-MPR, cation-independent mannose-6-phosphate receptor; CK, creatine kinase; CRIM, cross-reactive immunologic material; Creatine kinase; ERT, enzyme replacement therapy; Enzyme replacement therapy; GAA, acid alpha-glucosidase; GMFM, Gross Motor Function Measure; Glc4, glucose tetrasaccharide; IOPD, infantile-onset Pompe disease; LOPD, late-onset Pompe disease; MRI, magnetic resonance imaging; NBS, newborn screening; Pompe disease; SCT, 4-stair climb test; rhGAA, recombinant human GAA.