Pompe Disease
Conditions
Keywords
Pompe disease, Pyridostigmine
Brief summary
Pyridostigmine is an acetylcholinesterase inhibitor, which degrades acetylcholine at the neuromuscular junction. Based on recent studies, pyridostigmine may be an effective adjuvant treatment for people with Pompe disease, as it increases the functional impact of this neurotransmitter. Hypothesis: the use of pyridostigmine in Pompe disease will improve transmission of acetylcholine across the neuromuscular junction, skeletal muscle function, respiratory function, and quality of life.
Detailed description
Pompe is a rare disease, which occurs in approximately 1 per 40,000 births. It is a progressive and often fatal neuromuscular disorder resulting from mutation in the gene for acid alpha-glucosidase (GAA), an enzyme necessary to degrade glycogen. Accumulation of glycogen in multiple tissues results in cardiac, respiratory and skeletal muscle dysfunction. Enzyme replacement therapy (ERT) is currently the only treatment available, and although it prolongs survival, adjuvant therapies are needed to help alleviate the dire symptoms of Pompe disease. Recent data has revealed that degradation of the neuromuscular junction (NMJ) occurs in Pompe disease. Acetylcholinesterase inhibitors (AChEI) are substances that inhibit the AChE enzyme from degrading acetylcholine at the NMJ, and thus increase the functional impact of this neurotransmitter. AChEI are established as a beneficial therapy for individuals with primary diseases of the NMJ, such as myasthenia gravis. Recently, administration of an AChEI was demonstrated to improve NMJ pathology in both mice and individuals affected by other congenital myopathies, including autosomal centronuclear myopathies (CNM), X-linked myotubular myopathy (XLMTM) and mutation of tropomyosin 3 (TPM3). Specifically, both NMJ transmission and motor function were improved. These studies demonstrate that AChEI can be beneficial in myopathy associated with NMJ pathology. In this study, we will study the acute effects of pyridostigmine on neuromuscular transmission, as well as the prolonged effects on respiratory function, skeletal muscle function and quality of life over a 90 day treatment period. This project focuses on developing an adjuvant treatment to ERT that targets dysfunction at the NMJ. Our ultimate goal is to reduce the deleterious consequences of Pompe disease and improve the overall quality and duration of life in affected individuals.
Interventions
Pyridostigmine is an acetylcholinesterase inhibitor, which increases the amount of acetylcholine at the neuromuscular junction. It will be taken orally, either as a tablet or as a syrup.
Sponsors
University of Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females between 8 and 60 years of age; 2. Diagnosis of Pompe disease (protein assay, genotyping, and positive clinical signs) 3. No contraindication to pyridostigmine
Exclusion criteria
1. Already receive pyridostigmine as part of their normal clinical care at screening 2. Are pregnant - participants will receive a urine pregnancy test at screening 3. Have received acute administration of antibiotic, corticosteroid, or neuromuscular blockade medications within 30 days prior to screening 4. Any other concurrent medical condition which, in the opinion of the study team, would make the subject inappropriate to participate in the assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in skeletal muscle function (6 Minute Walk Test)(QMT) | Baseline, Day 90 | Quantitative muscle testing and the 6 Minute Walk Test will be used to evaluate skeletal muscle function. |
| Change in respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and vital capacity) | Baseline, Day 90 | Pulmonary function tests, including maximal inspiratory pressure, maximal expiratory pressure, and vital capacity, will be used to evaluate respiratory function |
| Change in quality of life [short form 36 (SF-36)] | Baseline, Day 90 | The short form 36 health survey (SF-36) will be used to evaluate quality of life |
| Evaluate the acute effects of pyridostigmine on neuromuscular junction transmission (Single-fiber EMG) | Baseline | Single-fiber EMG will be performed on the tibialis anterior pre- and 2 hour post-administration of pyridostigmine. MIP and hand grip will also be tested before and after receiving the study drug. |
Countries
United States
Outcome results
None listed