Pharmacological Chaperone Therapy for Pompe Disease

Borie-Guichot, M.; Tran, My Lan; Génisson, Yves; Ballereau, Stéphanie; Dehoux, Cécile

doi:10.3390/molecules26237223

Cited by 10 publications

(6 citation statements)

References 77 publications

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“…The limitations of ERT have stimulated the scientific community to investigate alternative therapeutic strategies against PD, independent or complementary to ERT. Among the therapies currently explored, gene therapy, substrate reduction therapy, and pharmacological chaperone (PC) therapy should be mentioned [61][62][63][64].…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

Risk of Cardiac Arrhythmias in Patients with Late-Onset Pompe Disease—Results from a Long Follow-Up in a Group of 12 Patients and Review of Literature

Palladino,

Passamano,

Scutifero

et al. 2024

Cardiogenetics

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Background. Pompe disease is a rare, severe, autosomal recessive genetic disorder caused by GAA gene mutations, which cause α-1,4-glucosidase enzyme deficiency. There are two forms of Pompe disease based on the age of onset, the infantile and the adult form (LOPD). Cardiac involvement, previously recognized only in infantile cases, is now also reported in adults. Cardiomyopathy remains an exceptional finding while heart rhythm disorders appear to be more frequent. Methods. We retrospectively evaluated cardiac involvement in 12 patients with late-onset Pompe disease (LOPD) followed for an overall period of 143 years (mean 12.7 ± 7.7) using ECG, Holter ECG, and echocardiography. Results. The mean age of patients (M8:F4) at the first visit was 40.7 ± 16.1 (range 14–63) and 53.7 ± 16.9 (range 21–76) at last visit. Conduction delay was present in three patients; one patient developed ascending aorta ectasia but had a history of hypertension, and one patient showed right heart enlargement on echocardiography, probably due to pulmonary hypertension. No patient died during the FU, nor developed cardiomyopathy. Ectopic supraventricular beats and repeated episodes of ablation-resistant atrial fibrillation were observed in only one patient (8.3%) who required PMK implantation. Conclusion. Benefitting from the long follow-up, this study allows us to state that primary myocardial involvement is rare in patients with LOPD, while rhythm disorders are more frequent and require monitoring to avoid the risk of possible life-threatening complications.

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Section: Diagnosis and Treatmentmentioning

confidence: 99%

Risk of Cardiac Arrhythmias in Patients with Late-Onset Pompe Disease—Results from a Long Follow-Up in a Group of 12 Patients and Review of Literature

Palladino,

Passamano,

Scutifero

et al. 2024

Cardiogenetics

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“…Pharmacological chaperone therapy (PCT), first experimented in treatment of Fabry disease, is based on the concept that small-molecule ligands may act by blocking conformational fluctuations of a partially misfolded protein, thereby facilitating its trafficking into organelles [ 175 , 176 ]. In 2007, the action of the chaperone deoxynojirimycin (DNJ) and its derivative, N-butyldeoxynojirimycin (NB-DNJ), on the fibroblasts of Pompe patients showed a significant increase in GAA activity in fibroblasts carrying particular mutations [ 177 , 178 ].…”

Section: Treatment Approachesmentioning

confidence: 99%

A Comprehensive Update on Late-Onset Pompe Disease

Labella,

Cotti Piccinelli,

Risi

et al. 2023

Biomolecules

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Pompe disease (PD) is an autosomal recessive disorder caused by mutations in the GAA gene that lead to a deficiency in the acid alpha-glucosidase enzyme. Two clinical presentations are usually considered, named infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), which differ in age of onset, organ involvement, and severity of disease. Assessment of acid alpha-glucosidase activity on a dried blood spot is the first-line screening test, which needs to be confirmed by genetic analysis in case of suspected deficiency. LOPD is a multi-system disease, thus requiring a multidisciplinary approach for efficacious management. Enzyme replacement therapy (ERT), which was introduced over 15 years ago, changes the natural progression of the disease. However, it has limitations, including a reduction in efficacy over time and heterogeneous therapeutic responses among patients. Novel therapeutic approaches, such as gene therapy, are currently under study. We provide a comprehensive review of diagnostic advances in LOPD and a critical discussion about the advantages and limitations of current and future treatments.

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“…A phase 2 co-administration study of chaperone AT2220 together with ERT is underway, too. 25 Chaperone therapy is currently evaluated as a therapeutic option in several single-gene disorders, including Pompe disease. Chaperone therapy enhances the activity of misfolded variants of GAA, the deficient enzyme involved in Pompe disease.…”

Section: Mutation Analysismentioning

confidence: 99%

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

Nagpal¹,

Goyal

Mathur

et al. 2023

Journal of Pediatric Neurology

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A high index of suspicion is required to diagnose rare genetic disorders, such as Pompe disease, with common clinical manifestations in children. There is a need to sensitize physicians regarding cues to early screening and diagnosis of such patients. Minimal epidemiological data are available on Pompe disease in India. The aim of this study was to determine the prevalence of Pompe disease in high-risk pediatric populations and determine the appropriateness of screening dried blood spot (DBS) tests to facilitate the diagnosis of Pompe disease. We screened pediatric patients presented with (1) unexplained hypotonia, respiratory distress, cardiomyopathy, and elevated liver function tests; and (2) unexplained limb girdle muscle weakness through a DBS test for enzyme assay. Those patients found positive underwent acid alpha-glucosidase mutational analysis. This prospective cross-sectional study was conducted in 45 suspected patients after approval from the institutional ethical committee. Of the 45 suspected patients, 9 (20%) were found to be positive by DBS test. Out of these nine tested, four (44.4%) were positive, two (22.2%) were negative, and three (33.3%) could not be tested for mutation analysis. The prevalence of genetically confirmed Pompe disease in high-risk populations was 8.8%. The results of this study show that clinical suspicion and DBS filter paper test facilitate early diagnosis and management, thereby improving the quality of life in patients. DBS test acts as a robust, rapid first-tier screening test for Pompe disease.

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Pharmacological Chaperone Therapy for Pompe Disease

Cited by 10 publications

References 77 publications

Risk of Cardiac Arrhythmias in Patients with Late-Onset Pompe Disease—Results from a Long Follow-Up in a Group of 12 Patients and Review of Literature

Risk of Cardiac Arrhythmias in Patients with Late-Onset Pompe Disease—Results from a Long Follow-Up in a Group of 12 Patients and Review of Literature

A Comprehensive Update on Late-Onset Pompe Disease

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

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