Trial findings were reported in the study, “Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease,” published in the journal Molecular Genetics and Metabolism.
“A five-year study of the benefits of ERT in patients with LOPD confirmed that benefits occurred in the first to to three years of treatment only, followed by a stability or a gradual decline,” the researchers wrote.
That may be caused by the lack of protein receptors that take up the replacement enzyme into muscle cells, leading to an insufficient amount of the enzyme inside these cells, they said.
A preclinical study showed that albuterol, a bronchodilator that is often used to treat conditions like asthma, can increase the levels of these receptors on muscle cells, as well the effectiveness of ERT in a mouse model of Pompe disease.
A pilot trial showed that albuterol significantly increased the distance walked during the six-minute walk test (6MWT, a common measure of motor function and functional capacity) in a small number of LOPD patients receiving ERT.
Researchers at Duke University School of Medicine, in collaboration with investigators at Sanofi Genzyme, reported the findings of a Phase 1/2 trial (NCT01885936) assessing the safety and efficacy of albuterol as an add-on therapy in LOPD patients receiving ERT.
The study, sponsored by Duke, enrolled 13 LOPD patients — three men and ten women — with an average age of 50, who had been on ERT for at least one year (more than five years for most participants).
Following enrollment, participants were randomly assigned to receive either albuterol or a placebo, both taken by mouth in addition to ERT, for a period of 24 weeks (approximately six months).
The study’s main goal was to assess the safety of albuterol. Secondary goals included assessing the efficacy of albuterol on lung and motor function.
One participant in the albuterol group withdrew from the trial after six weeks for unspecified reasons; the remaining participants completed the trial.
No serious adverse reactions associated with albuterol were reported during the study. Adverse events were generally mild, and included anxiety, tremors, and weight loss. The frequency of insomnia was higher in the albuterol group than in the placebo group (50% versus 20%).
After 24 weeks of treatment, the 6MWT distance in the albuterol group increased by 25 meters (about 82 feet) on average. This was accompanied by an improvement of 8% in the average score of the Gross Motor Function Measure (GMFM-88, a questionnaire that measures motor function).
There were also significant improvements in supine (lying-down) lung function, as measured by both forced expiratory volume (FEV1) and forced vital capacity (FVC). In the albuterol group, supine FVC increased by an average of 10%, and supine FEV1 by an average of 8%. There were no significant changes in upright FVC or FEV1.
“These data suggested that albuterol administration improved respiratory muscle strength,” the researchers wrote. The improvement in supine lung function is specifically noteworthy, they said, as there is a “known risk” for supine asphyxiation (suffocation while lying down) among LOPD patients, including those on ERT.
Unlike those in the albuterol group, LOPD patients receiving ERT alone did not show significant improvements in any outcome measure.
The study was a small one, done at a single center on a fairly homogeneous group of participants, so the extent to which its findings can be generalized is limited, the investigators noted. Nonetheless, the study provides support for the efficacy of albuterol as an add-on therapy to ERT in Pompe disease, and highlights the need for future research, they said.
“This study provides initial support for the safety and potential efficacy of albuterol ER [extended release] as an adjunctive therapy in Pompe disease, and justifies further development of [similar agents] for the treatment of Pompe disease,” the researchers said.
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