α-Glucosidase Deficiency (Pompe’s Disease)

Tager, J. M.; Elferink, Ronald P.J. Oude; Reuser, Arnold; Kroos, Marian A.; Ginsel, L.A.; Fransen, J.A.M.; Klumperman, Judith

doi:10.1159/000469217

Cited by 12 publications

(5 citation statements)

References 27 publications

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“…In a healthy person with normal enzyme activity, the function of this enzyme is to destroy the complex sugar melodies stored in lysosomes in cells. Therefore, insufficient or defective enzymes cannot eliminate the complex sugar molecules, so storage occurs [ 46 ]. Therefore, the presence of CS and CS cryogel does not affect the fractional activity of α-glucosidase and can be used in such applications.…”

Section: Resultsmentioning

confidence: 99%

Chondroitin Sulfate-Based Cryogels for Biomedical Applications

Demirci

Şahiner

Ari

et al. 2021

Gels

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Cryogels attained from natural materials offer exceptional properties in applications such as tissue engineering. Moreover, Halloysite Nanotubes (HNT) at 1:0.5 weight ratio were embedded into CS cryogels to render additional biomedical properties. The hemolysis index of CS cryogel and CS:HNT cryogels was calculated as 0.77 ± 0.41 and 0.81 ± 0.24 and defined as non-hemolytic materials. However, the blood coagulation indices of CS cryogel and CS:HNT cryogels were determined as 76 ± 2% and 68 ± 3%, suggesting a mild blood clotting capability. The maximum% swelling capacity of CS cryogel was measured as 3587 ± 186%, 4014 ± 184%, and 3984 ± 113%, at pH 1.0, pH 7.4 and pH 9.0, respectively, which were reduced to 1961 ± 288%, 2816 ± 192, 2405 ± 73%, respectively, for CS:HNT cryogel. It was found that CS cryogels can hydrolytically be degraded 41 ± 1% (by wt) in 16-day incubation, whereas the CS:HNT cryogels degraded by 30 ± 1 wt %. There is no chelation for HNT and 67.5 ± 1% Cu(II) chelation for linear CS was measured. On the other hand, the CS cryogel and CS:HNT cryogel revealed Cu(II) chelating capabilities of 60.1 ± 12.5%, and 43.2 ± 17.5%, respectively, from 0.1 mg/mL Cu(II) ion stock solution. Additionally, at 0.5 mg/mL CS, CS:HNT, and HNT, the Fe(II) chelation capacity of 99.7 ± 0.6, 86.2 ± 4.7% and only 11.9 ± 4.5% were measured, respectively, while no Fe(II) was chelated by linear CS chelated Fe(II). As the adjustable and controllable swelling properties of cryogels are important parameters in biomedical applications, the swelling properties of CS cryogels, at different solution pHs, e.g., at the solution pHs of 1.0, 7.4 and 9.0, were measured as 3587 ± 186%, 4014 ± 184%, and 3984 ± 113%, respectively, and the maximum selling% values of CS:HNT cryogels were determined as 1961 ± 288%, 2816 ± 192, 2405 ± 73%, respectively, at the same conditions. Alpha glucosidase enzyme interactions were investigated and found that CS-based cryogels can stimulate this enzyme at any CS formulation.

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Section: Resultsmentioning

confidence: 99%

Chondroitin Sulfate-Based Cryogels for Biomedical Applications

Demirci

Şahiner

Ari

et al. 2021

Gels

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“…However, the destruction of complex sugar molecules cannot occur due to this innately deficient or insufficient enzyme, and storage begins. Enzyme replacement therapy is one of the treatment methods applied [16,17]. Cross-linked particle forms of RUT were synthesized in our previous study [9].…”

Section: Alpha-glucosidase Enzyme Activity Assaymentioning

confidence: 99%

Poli(Rutin) micro/nanogels for biomedical applications

Şahiner¹,

Suner²

2021

Hittite J. Sci. Eng.

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I nterest in flavonoids, which are phenolic compounds, has grown with the French paradox. Interest in bioflavonoids has increased based on Mediterranean culture, which includes a diet rich in phenol directly proportional to high fat with an inverse relationship with the risk of heart attack. Flavonoids are widely used in the food industry due to antioxidant and antimicrobial properties. Flavonoids are known to affect many biofunctions such as lowering blood pressure and having anti-inflammatory, hypocholesterolemic, anticancer platelet stabilizer, antiallergic, antidepressant and blood clotting properties [1,2]. Rutin is a known flavonoid and has two sugar molecules in its structure. Rutin's chemical name is quercetin-3-remnosyl glucoside [3]. It is present in many fruits and vegetables such as onion, tea, apple, parsley, citrus, sage, and grape [4]. It is used in the food, cosmetics, and even pharmacology industries

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“…Genetic deficiency of the lysosomal acid maltase or acid α-glucosidase (GAA) results in acid maltase deficiency (AMD) or Pompe disease (PD) encompassing at least four clinical subtypes of varying severity (infantile; childhood, juvenile and adult onset) (1). PD exhibits intracellular accumulation of glycogen in multiple tissues with skeletal muscle being the primary target, manifesting as myopathy and cardiomyopathy (2)(3)(4)(5). The classic infantile form (IOPD) exhibits no enzyme activity, muscle weakness, feeding difficulties and hypertrophic cardiomyopathy, leading to death in the first year (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Preclinical studies with ground germinated barley (GGB) for oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice

Martiniuk,

Mack,

Martiniuk

et al. 2023

Preprint

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Genetic deficiency of lysosomal acid maltase or acid α-glucosidase (GAA) results in the orphan disease known as glycogen storage disease type II or acid maltase deficiency (AMD) or Pompe disease (PD), encompassing at least four clinical subtypes of varying severity. PD results from mutations in theGAAgene and deficient GAA activity, resulting in the accumulation of glycogen in tissues (primarily muscle) and characterized by progressive skeletal muscle weakness and respiratory insufficiency. The current approved enzyme replacement therapy (ERT) for PD is via intravenous infusion of a recombinant human GAA (rhGAA) secreted by CHO cells (Myozyme, Sanofi-Genzyme) given once every 2 weeks and has shown varying efficacy in patients. Although the current ERT has proven to be very efficient in rescuing cardiac abnormalities and extending the life span of infants, the response in skeletal muscle is variable. In late-onset patients, only mild improvements in motor and respiratory functions have been achieved and the current ERT is unsatisfactory in the reversal of skeletal muscle pathology. Additional challenges for ERT include insufficient targeting/uptake of enzyme into disease-relevant tissues, poor tolerability due to severe ERT-mediated anaphylactic and immunologic reactions and the prohibitively high cost of lifelong ERT ($250-500K/year adult patient). A consensus at a Nov.-2019 US Acid Maltase Deficiency Association conference suggested that a multi-pronged approach including gene therapy, diet, exercise, etc. must be evaluated for a successful treatment. Our objective is to develop an innovative and affordable approach via barley GAA (bGAA) from ground germinated barley (GGB) or liquid GGB (L-GGB) for Oral-ERT for PD or as a daily supplement to Myozyme. To this end, we hypothesize that a bGAA produced in germinated barley can be ingested daily that allows the maintenance of a therapeutic level of enzyme. We have shown in extensive preliminary data thatGGBorL-GGBwas (1) enzymatically active, (2) was taken up by GAA KO mice and human WBCs to reverse the enzyme defect that was blocked by mannose-6-phosphate, (3) hydrolyzed glycogen, (4) increased significant changes in the clinical phenotype towards the WT levels in GAA KO mice dose-dependently, (5) taken up by PD myoblasts, lymphoid/fibroblasts cells to reverse the defect, (6) bGAA was ∼70kD, (7) Km, Vmax, pH optima, inhibitors and kinetics was similar to human placental GAA and an rhGAA and (8) was strain specific.

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α-Glucosidase Deficiency (Pompe’s Disease)

Cited by 12 publications

References 27 publications

Chondroitin Sulfate-Based Cryogels for Biomedical Applications

Chondroitin Sulfate-Based Cryogels for Biomedical Applications

Poli(Rutin) micro/nanogels for biomedical applications

Preclinical studies with ground germinated barley (GGB) for oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice

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