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Hurler disease/mucopolysaccharidosis type IH (MPSIH)/α-L-iduronidase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Enzyme replacement with human recombinant α-L-iduronidase has been reported [52, 53] in 45 patients with MPS I. Patients were selected with Hurler-Scheie or Scheie phenotypes and given enzyme intravenously weekly for as long as 62 weeks. Hepatosplenomegaly decreased significantly in all patients. Liver size was normal in eight patients by 26 weeks. Growth in height and weight increased in prepubertal patients. Improvements were also notable in the urinary excretion of glycosaminoglycans, as well as in joint mobility, respiratory function (forced vital capacity) [52, 53], and ambulation (6-minute walk test). The enzyme has now been approved by the US Food and Drug Administration (FDA) (in 2003) and is marketed as Aldurazyme (BioMarin Genzyme). Corneal clouding does not change; valvular disease seems to be unaltered. There is little likelihood that this approach would affect the brain; trials are underway to treat with intrathecal enzyme [54]. Enzyme replacement therapy has been used for a sufficient number of years in the treatment of Hurler disease to establish that it is efficacious in reducing biochemical characteristics of the disease such as urinary glycosaminoglycan excretion and improved function capacity, as well as liver size [55].
Role of Engineered Proteins as Therapeutic Formulations
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Khushboo Gulati, Krishna Mohan Poluri
Enzymes are the catalysts that aid in carrying out various complex chemical reactions. Enzymes are being used as therapeutics since long time. Previously, proteolytic enzymes were employed as supplements in the treatment of gastrointestinal related disorders. Nowadays, enzymes are being exploited in the treatment of various types of cancers and numerous other diseases. Collagenase, a collagen degrading enzyme breaks peptide bonds in collagen. Microbial collagen is being used in debridement of ulcers and burns (Ramundo and Gray, 2008; Ramundo and Gray, 2009). Collagenase is also used for enzymatic fasciotomy owing to its specificity for collagen. Collagenase derived from Clostridium histolyticum is used as nonsurgical treatment for Dupuytren’s contracture, as approved by US FDA (Coleman et al., 2014). Pancreatic exocrine insufficiency (PEI) is a condition related to pancreatic diseases such as chronic pancreatitis, and cystic fibrosis. This disease leads to the weight loss, malnutrition, morbidity, and mortality. Pancreatic enzyme replacement therapy (PERT) is used to address the pathophysiological conditions in PEI (Nakajima et al., 2012). PERT is also used in patients suffering from cystic fibrosis (Somaraju and Solis-Moya, 2014). Many other diseases including genetic disorders are being treated by the strategy of ERT. ERT has been approved by FDA. Some notable ERT’s include Fabrazyme® (agalsidase beta) for Fabry Disease (Borgwardt et al., 2013); Elelyso™ (taliglucerase) (Haddley, 2012), VPRIV™ (velaglucerasealfa) (Hughes et al., 2015) for type I Gaucher disease; Aldurazyme® (laronidase) for MPS I (Hurler, Hurler-Scheie, or Scheie syndrome) (Jameson et al., 2013); Lumizyme® (alglucosidasealfa) for Glycogen Storage Disease type II (Pompe disease); Naglazyme™ (galsulfase) for MPS VI (Maroteaux-Lamy syndrome) (Brunelli et al., 2016), Elaprase® (idursulfase intravenous) for MPS II (Hunter disease) (Burrow and Leslie, 2008). ERT approach is not devoid of limitations, it is also associated with high production cost and lower bioavailability. Hence, continuous efforts are being made in these directions to circumvent these limitations.
OCT imaging of macular cysts and treatment response with nepafenac in mucopolysaccharidosis type 1
Published in Ophthalmic Genetics, 2023
Aslıhan Yılmaz Çebi, Mustafa Hepokur
A 27-year-old female with mucopolysaccharidosis type I (MPS I) was referred to our clinic. She had blurry vision for one month. She was diagnosed with MPS I (Scheie phenotype) ten years ago and was treated with enzyme replacement therapy (ERT) with alpha-L-iduronidase (Aldurazyme) at a weekly dose of 0.58 mg/kg for ten years. The best-corrected visual acuity in both eyes was 20/25 (refraction was +7.00D–4.00x155 OD and +7.25D–4.25x17 OS). Both cornea were clear, despite the presence of guttata on specular microscopy. There was no trace of cataract formation. Dilated fundus examination revealed bilateral pigmentary retinopathy, and fine radial abnormalities on the superotemporal side of macula (Figure 1). Optical coherence tomography (OCT) showed macular cysts in the inner and outer nuclear layers (INL and ONL) and central external limiting membrane thickening (Figure 2). The perifoveal ellipsoid zone and the IS/OS line have been preserved. Fluorescein angiography (FA) did not show any evidence of vascular dye leakage (Figure 3).
The potential of gene therapy for mucopolysaccharidosis type I
Published in Expert Opinion on Orphan Drugs, 2020
Luisa Natalia Pimentel Vera, Guilherme Baldo
Currently, there are two different treatments for MPS I patients available. The first one is enzyme replacement therapy (ERT), approved for human use in 2003 (Aldurazyme®, Sanofi/Genzyme). This enzyme is a human recombinant variant of IDUA produced in CHO cells, that displays human-like post-translational modifications that allow cross–correction after intravenous administration [7,12]. Patients that received treatment showed variate responses. It is an exogenous enzyme, therefore, antibody production has been detected in almost every patient. Also, side effects such as anaphylactic reactions have been described. The treatment has demonstrated positive outcomes as the significant reduction in secreted urinary GAGs, spleen and liver volume. Nevertheless, cardiac alterations, pulmonary function and joint motility show only limited improvement, and brain abnormalities are not corrected due to the inability of the enzyme to reach the central nervous system [12,13].