Enzyme replacement therapies: what is the best option?

Safary, Azam; Akbarzadeh-Khiavi, Mostafa; Mousavi, Rahimeh; Barar, Jaleh; Rafi, Mohammad

doi:10.15171/bi.2018.17

Cited by 48 publications

(35 citation statements)

References 44 publications

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“…Although erT has provided an effective treatment for patients with some lSDs, it has limitations. recombinant enzymes administered by intravenous injection are not able to cross the blood-brain barrier, and so are not effective for central nervous system manifestations of lSDs 201 . low expression of the receptors that mediate delivery on the cell surface of target cells can also be a challenge for the effectiveness of erT for some lSDs 46 .…”

Section: Wwwnaturecom/nrdmentioning

confidence: 99%

Lysosomes as a therapeutic target

Bonam

Wang

Muller

2019

Nat Rev Drug Discov

546

374

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| Lysosomes are membrane-bound organelles with roles in processes involved in degrading and recycling cellular waste, cellular signalling and energy metabolism. Defects in genes encoding lysosomal proteins cause lysosomal storage disorders, in which enzyme replacement therapy has proved successful. Growing evidence also implicates roles for lysosomal dysfunction in more common diseases including inflammatory and autoimmune disorders, neurodegenerative diseases, cancer and metabolic disorders. With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases -including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease -this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs.

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Section: Wwwnaturecom/nrdmentioning

confidence: 99%

Lysosomes as a therapeutic target

Bonam

Wang

Muller

2019

Nat Rev Drug Discov

546

374

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“…[14][15][16] Among different types of NSs, the greater affinity, specificity, and functionality of enzymes to selectively target the desired cells/tissues make them prominent treatment modalities for a variety of diseases. [17][18][19][20] Bovine pancreatic ribonuclease A (RNase A, EC:3.1.27.5) is one of the best characterized small proteins (13.7 kDa), which was investigated for therapeutical purposes as a potential anticancer modality in 1972. 21 RNases represent a new class of cytotoxic and non-mutagenic enzymes, that can inhibit the proliferation of cancer cells through the catalytic cleavage of phosphodiester bonds in various types of single-stranded RNA (e.g., tRNA, rRNA, mRNA, and non-coding RNA), and hence, influence several signaling pathways, as well as protein biosynthesis at transcription and translation stages.…”

Section: Synthesis Of Peg Ligands Sh-peg-coohmentioning

confidence: 99%

PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells

et al. 2019

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Introduction: Currently, drug-induced reactive oxygen species (ROS) mediating apoptosis pathway have extensively been investigated in designing effective strategies for colorectal cancer (CRC) chemotherapy. Bovine pancreatic ribonuclease A (RNase A) represents a new class of cytotoxic and non-mutagenic enzymes, and has gained more attention as a potential anticancer modality; however, the cytosolic ribonuclease inhibitors (RIs) restrict the clinical application of this enzyme. Nowadays, nanotechnology-based diagnostic and therapeutic systems have provided potential solutions for cancer treatments. Methods: In this study, the gold nanoparticles (AuNPs) were synthesized, stabilized by polyethylene glycol (PEG), functionalized, and covalently conjugated with RNase A. The physicochemical properties of engineered nanobiomedicine (AuNPs-PEG-RNase A) were characterized by scanning electron microscope (SEM), dynamic light scattering (DLS), and UV-vis spectrum. Then, its biological impacts including cell viability, apoptosis, and ROS production were evaluated in the SW-480 cells. Results: The engineered nanobiomedicine, AuNPs-PEG-RNase A, was found to effectively induce apoptosis in SW-480 cells and result in a significant reduction in cancer cell viability. Besides, the maximum production of ROS was obtained after the treatment of cells with an IC50 dose of AuNPs-PEG-RNase A. Conclusion: Based on the efficient ROS-responsiveness and the anticancer activity of RNase A of the engineered nanomedicine, this nanoscaled biologics may be considered as a potential candidate for the treatment of CRC.

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“…Among therapeutic proteins, enzymes represent a small but rapidly growing market due to their potential application in curing important, rare, and deadly diseases. For example, enzyme replacement therapy (ERT) is undoubtedly the most promising therapeutic approach for mucopolysaccharidosis (MPSs), as well as for some other forms of lysosomal storage disorders (LSDs) such as Gaucher disease [ 1 ], Fabry disease [ 2 ], and Pompe disease [ 3 ], in which remarkable clinical benefits are currently obtained [ 4 ]. Unfortunately, clinical applications of these macromolecules are hampered by numerous obstacles to their successful delivery and targeting.…”

Section: Introductionmentioning

confidence: 99%

Enzyme Stability in Nanoparticle Preparations Part 1: Bovine Serum Albumin Improves Enzyme Function

et al. 2020

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Enzymes have gained attention for their role in numerous disease states, calling for research for their efficient delivery. Loading enzymes into polymeric nanoparticles to improve biodistribution, stability, and targeting in vivo has led the field with promising results, but these enzymes still suffer from a degradation effect during the formulation process that leads to lower kinetics and specific activity leading to a loss of therapeutic potential. Stabilizers, such as bovine serum albumin (BSA), can be beneficial, but the knowledge and understanding of their interaction with enzymes are not fully elucidated. To this end, the interaction of BSA with a model enzyme B-Glu, part of the hydrolase class and linked to Gaucher disease, was analyzed. To quantify the natural interaction of beta-glucosidase (B-Glu,) and BSA in solution, isothermal titration calorimetry (ITC) analysis was performed. Afterwards, polymeric nanoparticles encapsulating these complexes were fully characterized, and the encapsulation efficiency, activity of the encapsulated enzyme, and release kinetics of the enzyme were compared. ITC results showed that a natural binding of 1:1 was seen between B-Glu and BSA. Complex concentrations did not affect nanoparticle characteristics which maintained a size between 250 and 350 nm, but increased loading capacity (from 6% to 30%), enzyme activity, and extended-release kinetics (from less than one day to six days) were observed for particles containing higher B-Glu:BSA ratios. These results highlight the importance of understanding enzyme:stabilizer interactions in various nanoparticle systems to improve not only enzyme activity but also biodistribution and release kinetics for improved therapeutic effects. These results will be critical to fully characterize and compare the effect of stabilizers, such as BSA with other, more relevant therapeutic enzymes for central nervous system (CNS) disease treatments.

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Enzyme replacement therapies: what is the best option?

Cited by 48 publications

References 44 publications

Lysosomes as a therapeutic target

Lysosomes as a therapeutic target

PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells

Enzyme Stability in Nanoparticle Preparations Part 1: Bovine Serum Albumin Improves Enzyme Function

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