Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.
Abstract
Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher
than for other lysosomal storage disorders, which has been attributed to low cation-independent
mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated
the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase
during ERT in mice with Pompe disease following addition of albuterol therapy. Currently
we have completed a pilot study of albuterol in patients with late-onset Pompe disease
already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT)
distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004),
and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved
significantly for both hands at wk 12. Furthermore, individual subjects reported benefits;
e.g., a female patient could stand up from sitting on the floor much more easily (time
for supine to standing position decreased from 30 to 11 s), and a male patient could
readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on
manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased
CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient
who succumbed to respiratory complications of Pompe disease in the first week, only
mild adverse events have been reported, including tremor, transient difficulty falling
asleep, and mild urinary retention (requiring early morning voiding). Therefore, this
pilot study revealed initial safety and efficacy in an open label study of adjunctive
albuterol therapy in patients with late-onset Pompe disease who had been stable on
ERT with no improvements noted over the previous several years.
Type
Journal articleSubject
acid maltaseacid α-glucosidase
glycogen storage disease type II
mannose-6-phosphate receptor
Adrenergic beta-2 Receptor Agonists
Albuterol
Biopsy
Electrocardiography
Enzyme Replacement Therapy
Female
Glycogen Storage Disease Type II
Hand Strength
Humans
Male
Muscle, Skeletal
Pilot Projects
Quadriceps Muscle
Receptor, IGF Type 2
Time Factors
Treatment Outcome
Walking
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https://hdl.handle.net/10161/10804Published Version (Please cite this version)
10.1096/fj.13-241893Publication Info
Koeberl, Dwight D; Austin, Stephanie; Case, Laura E; Smith, Edward C; Buckley, Anne
F; Young, Sarah P; ... Kishnani, Priya S (2014). Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset
Pompe disease. FASEB J, 28(5). pp. 2171-2176. 10.1096/fj.13-241893. Retrieved from https://hdl.handle.net/10161/10804.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Deeksha Sarihyan Bali
Professor of Pediatrics
1)Development of new non-invasive laboratory diagnostic methods using enzymology and
molecular diagnostic techniques for Glycogen Storage Diseases (GSDs) and Lysosomal
Storage Diseases (LSDs) like Pompe, Fabry, Gaucher, MPS - for early diagnosis and
treatment modalities. Exploration of new high throughput diagnostic platforms with
an idea of implementation into New born screening (NBS)of these diseases. 2)Clinical
research studies associated with Pompe disease with a goal to improve
Anne Frances Buckley
Associate Professor of Pathology
My basic research focus is on neurogenic stem cells and their involvement in brain
development and brain tumors. I work in mouse models using inducible in vivo genetic
systems, live imaging, and tissue culture, in addition to histological and biochemical
methods. My clinical research interests include neuromuscular diseases. I collaborate
with colleagues at Duke on basic and translational research in this area.
Laura Elizabeth Case
Associate Professor in Orthopaedic Surgery
Laura E Case, PT, DPT, MS, PCS, C/NDT is a board-certified clinical specialist in
pediatric physical therapy. She has dedicated her career to teaching, research in
childhood-onset neuromusculoskeletal disorders, and to the lifelong treatment of people
with childhood-onset neurological and neuromuscular disorders such as cerebral palsy,
traumatic brain injury, Duchenne muscular dystrophy, spinal muscular atrophy, Pompe
disease, myelodysplasia, juvenile rheumatoid arthriti
Priya Sunil Kishnani
Chen Family Distinguished Professor of Pediatrics
RESEARCH INTERESTS A multidisciplinary approach to care of individuals with genetic
disorders in conjunction with clinical and bench research that contributes to: 1)
An understanding of the natural history and delineation of long term complications
of genetic disorders with a special focus on liver Glycogen storage disorders, lysosomal
disorders with a special focus on Pompe disease, Down syndrome and hypophosphatasia2) )
The development of new therapies such
Dwight D. Koeberl
Professor of Pediatrics
As a physician-scientist practicing clinical and biochemical genetics, I am highly
motivated to seek improved therapy for my patients with inherited disorders of metabolism.
The focus of our research has been the development of gene therapy with adeno-associated
virus (AAV) vectors, most recently by genome editing with CRISPR/Cas9. We have developed
gene therapy for inherited disorders of metabolism, especially glycogen storage disease
(GSD) and phenylketonuria (PKU). 1) GSD
Edward Clinton Smith
Professor of Pediatrics
My clinical research interests focus on neuromuscular diseases. Neuromuscular diseases
are a large group of disorders with various causes sharing one common feature: weakness.
One large group of neuromuscular diseases is caused by abnormalities in the nerves
as they exit the brain stem and spinal cord and travel out to their respective muscles.
These are called “neuropathies.” Common examples in this group include
spinal muscular
Sarah Phyllis Young
Professor of Pediatrics
As a clinical biochemical geneticist and a director of the Duke Biochemical Genetics
laboratory, my research interests are focused on improving laboratory diagnostics
for rare inherited disorders of metabolism. I am actively involved in the development
of assays using mass spectrometry and other analytical techniques. My current research
on biomarkers for lysosomal storage disorders, such as Fabry and Pompe disease and
the mucopolysaccharidoses includes monitoring the response to novel ther
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