scholarly journals The Respiratory Phenotype of Pompe Disease Mouse Models

2020 ◽  
Vol 21 (6) ◽  
pp. 2256
Author(s):  
Anna F. Fusco ◽  
Angela L. McCall ◽  
Justin S. Dhindsa ◽  
Lucy Zheng ◽  
Aidan Bailey ◽  
...  
Keyword(s):  
Mouse Models ◽  
Pompe Disease ◽  
Neuromuscular Junctions ◽  
Respiratory Control ◽  
Glycogen Storage ◽  
Respiratory Dysfunction ◽  
Glycogen Accumulation ◽  
Search Terms ◽  
Respiratory Pathology

Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA), a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease mouse models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts that characterize the respiratory phenotype of Pompe mouse models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease mouse models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, higher-order respiratory control centers, phrenic and hypoglossal motor nuclei, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.

scholarly journals The Respiratory Phenotype of Pompe Disease Rodent Models

2020 ◽  
Author(s):  
Anna Fusco ◽  
Angela McCall ◽  
Justin Dhindsa ◽  
Lucy Zheng ◽  
Aidan Bailey ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Neuromuscular Junctions ◽  
Respiratory Control ◽  
Glycogen Storage ◽  
Motor Nucleus ◽  
Rodent Models ◽  
Respiratory Dysfunction ◽  
Glycogen Accumulation ◽  
Search Terms ◽  
Respiratory Pathology

Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA) – a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease rodent models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts which characterize the respiratory phenotype of Pompe rodent models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease rodent models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, phrenic and hypoglossal motor nucleus, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle and higher order respiratory control centers. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.

scholarly journals A Systematic Review and Meta-Analysis of Enzyme Replacement Therapy in Late-Onset Pompe Disease

2021 ◽  
Vol 10 (21) ◽  
pp. 4828
Author(s):  
Alícia Dorneles Dornelles ◽  
Ana Paula Pedroso Junges ◽  
Tiago Veiga Pereira ◽  
Bárbara Corrêa Krug ◽  
Candice Beatriz Treter Gonçalves ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pompe Disease ◽  
Late Onset ◽  
Meta Analysis ◽  
Glycogen Storage ◽  
Enzyme Replacement ◽  
Sf 36 ◽  
Glycogen Storage Disorder

Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD). Methods: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed. Results: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change −2.64 h (95% CI −5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases. Conclusion: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102.

scholarly journals Newborn Screening for Pompe Disease

2020 ◽  
Vol 6 (2) ◽  
pp. 31
Author(s):  
Takaaki Sawada ◽  
Jun Kido ◽  
Kimitoshi Nakamura
Keyword(s):  
Enzyme Activity ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Autosomal Recessive Disorder ◽  
Glycogen Storage Disease Type ◽  
Dried Blood Spots ◽  
Glycogen Storage ◽  
Glycogen Accumulation ◽  
Enzyme Replacement ◽  
Asian Populations

Glycogen storage disease type II (also known as Pompe disease (PD)) is an autosomal recessive disorder caused by defects in α-glucosidase (AαGlu), resulting in lysosomal glycogen accumulation in skeletal and heart muscles. Accumulation and tissue damage rates depend on residual enzyme activity. Enzyme replacement therapy (ERT) should be started before symptoms are apparent in order to achieve optimal outcomes. Early initiation of ERT in infantile-onset PD improves survival, reduces the need for ventilation, results in earlier independent walking, and enhances patient quality of life. Newborn screening (NBS) is the optimal approach for early diagnosis and treatment of PD. In NBS for PD, measurement of AαGlu enzyme activity in dried blood spots (DBSs) is conducted using fluorometry, tandem mass spectrometry, or digital microfluidic fluorometry. The presence of pseudodeficiency alleles, which are frequent in Asian populations, interferes with NBS for PD, and current NBS systems cannot discriminate between pseudodeficiency and cases with PD or potential PD. The combination of GAA gene analysis with NBS is essential for definitive diagnoses of PD. In this review, we introduce our experiences and discuss NBS programs for PD implemented in various countries.

Providing the conduit for treatment: The impact of vascular access and vein preservation in a 5-year-old child with prenatally diagnosed CRIM-negative Infantile Pompe disease

2021 ◽  
pp. 112972982199948
Author(s):  
Matthew Ostroff ◽  
Punita Gupta ◽  
Daniel Garcia
Keyword(s):  
Vascular Access ◽  
Pompe Disease ◽  
Disease Patient ◽  
Tolerance Induction ◽  
Glycogen Storage ◽  
Glycogen Accumulation ◽  
Enzyme Replacement ◽  
Infantile Pompe Disease ◽  
Glycogen Storage Disorder ◽  
The Impact

Pompe disease is an autosomal recessive glycogen storage disorder resulting in progressive glycogen accumulation expressed in infancy with cardiomyopathy and skeletal myopathy. Without treatment by enzyme replacement therapy (ERT), life expectancy is less than 2 years. The cross-reactive immunologic material (CRIM) positive or negative status is the basis for the response to ERT. CRIM-negative patients mount an immune response to ERT, making this the most dangerous presentation. The following case study describes the 5-year course of the first successful treatment of an in utero CRIM-negative Pompe disease patient with prophylactic immune tolerance induction (ITI) and administration of ERT given within the first 2 days of life followed by ultrasound guided vascular access that facilitated by bi-weekly infusions and extensive phlebotomy.

scholarly journals Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase

2017 ◽  
Vol 9 (418) ◽  
pp. eaam6375 ◽  
Author(s):  
Francesco Puzzo ◽  
Pasqualina Colella ◽  
Maria G. Biferi ◽  
Deeksha Bali ◽  
Nicole K. Paulk ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Therapeutic Potential ◽  
Scale Up ◽  
Glycogen Storage Disease Type ◽  
Neuromuscular Disorder ◽  
The Body ◽  
Respiratory Dysfunction ◽  
Glycogen Accumulation ◽  
Enzyme Replacement ◽  
Hepatic Expression

Glycogen storage disease type II or Pompe disease is a severe neuromuscular disorder caused by mutations in the lysosomal enzyme, acid α-glucosidase (GAA), which result in pathological accumulation of glycogen throughout the body. Enzyme replacement therapy is available for Pompe disease; however, it has limited efficacy, has high immunogenicity, and fails to correct pathological glycogen accumulation in nervous tissue and skeletal muscle. Using bioinformatics analysis and protein engineering, we developed transgenes encoding GAA that could be expressed and secreted by hepatocytes. Then, we used adeno-associated virus (AAV) vectors optimized for hepatic expression to deliver the GAA transgenes to Gaa knockout (Gaa−/−) mice, a model of Pompe disease. Therapeutic gene transfer to the liver rescued glycogen accumulation in muscle and the central nervous system, and ameliorated cardiac hypertrophy as well as muscle and respiratory dysfunction in the Gaa−/− mice; mouse survival was also increased. Secretable GAA showed improved therapeutic efficacy and lower immunogenicity compared to nonengineered GAA. Scale-up to nonhuman primates, and modeling of GAA expression in primary human hepatocytes using hepatotropic AAV vectors, demonstrated the therapeutic potential of AAV vector–mediated liver expression of secretable GAA for treating pathological glycogen accumulation in multiple tissues in Pompe disease.

scholarly journals Modeling CNS Involvement in Pompe Disease Using Neural Stem Cells Generated from Patient-Derived Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 8
Author(s):  
Yu-Shan Cheng ◽  
Shu Yang ◽  
Junjie Hong ◽  
Rong Li ◽  
Jeanette Beers ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pompe Disease ◽  
Drug Efficacy ◽  
Cns Involvement ◽  
Glycogen Accumulation ◽  
Induced Pluripotent ◽  
Alpha Glucosidase

Pompe disease is a lysosomal storage disorder caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene. Acid alpha-glucosidase deficiency leads to abnormal glycogen accumulation in patient cells. Given the increasing evidence of central nervous system (CNS) involvement in classic infantile Pompe disease, we used neural stem cells, differentiated from patient induced pluripotent stem cells, to model the neuronal phenotype of Pompe disease. These Pompe neural stem cells exhibited disease-related phenotypes including glycogen accumulation, increased lysosomal staining, and secondary lipid buildup. These morphological phenotypes in patient neural stem cells provided a tool for drug efficacy evaluation. Two potential therapeutic agents, hydroxypropyl-β-cyclodextrin and δ-tocopherol, were tested along with recombinant human acid alpha-glucosidase (rhGAA) in this cell-based Pompe model. Treatment with rhGAA reduced LysoTracker staining in Pompe neural stem cells, indicating reduced lysosome size. Additionally, treatment of diseased neural stem cells with the combination of hydroxypropyl-β-cyclodextrin and δ-tocopherol significantly reduced the disease phenotypes. These results demonstrated patient-derived Pompe neural stem cells could be used as a model to study disease pathogenesis, to evaluate drug efficacy, and to screen compounds for drug discovery in the context of correcting CNS defects.

scholarly journals The use of fentanyl in pain management in head and neck cancer patients: a narrative review

2017 ◽  
Vol 12 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Raffaele Giusti ◽  
Paolo Bossi ◽  
Marco Mazzotta ◽  
Marco Filetti ◽  
Daniela Iacono ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Head And Neck ◽  
Relative Effectiveness ◽  
Malignant Tumours ◽  
Exclusion Criteria ◽  
Search Terms ◽  
Strong Opioids ◽  
Cross Reference

Background: Head and neck (H&N) cancers account for about 5% of all malignant tumours. Pain is one of the most feared consequences of H&N neoplasms and is experienced by up to 80% of patients and worsens their quality of life inhibiting speaking, eating, drinking or swallowing. Nevertheless, pain is still often underestimated and undertreated. Objectives: The role of opioids in cancer pain has been well established but evidences about the role and the relative effectiveness of opioids such as fentanyl in the context of H&N cancer pain remains unclear. Methods: A literature review based on the guidance of the Centre for Reviews and Dissemination was conducted. An iterative approach was used starting with an electronic search in the MEDLINE database. The search terms ((‘Neoplasms’[Mesh]) AND ‘Head and Neck Neoplasms’[Mesh]) AND ‘Fentanyl’[Mesh] were used. Results: A total of 18 publications were found by the first performed search on PubMed. Other publications concordant with our aim were found by cross-reference. Considering inclusion and exclusion criteria for our review, eight papers resulted eligible for analysis. Conclusion: Fentanyl transdermal therapeutic system (TTS) seems to be an important option, thanks to the way of administration, the good safety and tolerability profiles to control baseline pain. For breakthrough cancer pain (BTcP), several formulations of transmucosal fentanyl are available. All the formulations seem to be active and safety but we lack head-to-head studies of fentanyl versus other strong opioids, as well as with different formulation of fentanyl, particularly for BTcP where H&N cancer population is very poorly represented.

A Quality Assessment of Online Patient Information Regarding Rhinoplasty

2021 ◽  
Author(s):  
Eamon Shamil ◽  
Gabriela Di Scenza ◽  
Shahi Abdul Ghani ◽  
Ka Siu Fan ◽  
Suthaharan Ragulan ◽  
...  
Keyword(s):  
Patient Information ◽  
Poor Quality ◽  
Complication Rates ◽  
Eligibility Criteria ◽  
Risks And Benefits ◽  
Search Terms ◽  
Outcome Management ◽  
Balanced Information ◽  
Unrealistic Expectations

AbstractThere is a large demand for online patient information for patients considering rhinoplasty. While there are many resources available, the quality and content of the information provided are unknown. This study aimed to assess the quality of the most popular information available online, using the “Ensuring Quality Information for Patients” (EQIP) tool to evaluate the content, structure, and readability of patient information on websites. Search terms including nose operation, nose job, nose reshaping, nose tip surgery, rhinoplasty, septorhinoplasty, were identified using Google AdWords and Trends. Unique links from the first 10 pages for each term were identified and evaluated with websites written in English and for general non-medical public use were included. 295 websites met the eligibility criteria with a median overall EQIP score of 17. Only 33% contained balanced information on the risks and benefits. Bleeding and infection risk was only mentioned in 29% and 27% of websites, respectively. Two percent described complication rates of the procedures and only 20% of articles explained further surgery may be required to achieve patient cosmetic or functional satisfaction. Information regarding rhinoplasty available online is currently of poor quality. The lack of effective risk counselling, possible outcome management, and complications may likely lead to unrealistic expectations of rhinoplasty. It is crucial the risks of surgery are communicated to the patient to ensure they can make an informed decision. Improved education through online resources would likely help to promote more realistic patient expectations.

Baduanjin Exercise for Adults Aged 65 Years and Older: A Systematic Review and Meta-Analysis of Randomized Controlled Studies

2021 ◽  
pp. 073346482110593
Author(s):  
Cindy Jones ◽  
Meiling Qi ◽  
Zihui Xie ◽  
Wendy Moyle ◽  
Benjamin Weeks ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Mainland China ◽  
Walking Ability ◽  
Search Terms ◽  
Randomized Controlled Studies ◽  
Chinese Studies ◽  
Older Chinese

This study performed a systematic review and meta-analysis to evaluate the health effects of Baduanjin exercise on adults aged 65 years and older. Chinese and English databases were electronically searched using search terms related to the PICO model from inception through June 2021. The study quality assessment and meta-analysis were conducted using the PEDro scale and RevMan 5.4 software. Eleven included Chinese studies, published between 2015 and 2021, recruited participants from the mainland of China. The aggregated results showed significant benefits of Baduanjin on physical function, walking ability, balance, and anxiety. A long-term Baduanjin intervention could also improve quality of life and reduce falls and pain. Baduanjin appears to have the potential to improve the health of older adults, but conclusions are limited due to the lack of rigorous and robust studies within and outside of mainland China. Larger, well-designed RCTs are needed to confirm these findings.

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