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Advances in Genome Editing
Published in Yashwant Pathak, Gene Delivery, 2022
Schuh and co-workers studied targeting of CRISPR/Cas9 and a donor oligonucleotide aiming at Mucopolysaccharidosis type I gene editing in vitro. The DNA were complexed with nanoemulsions, which showed effective introduction into MPS I p.Trp402∗ patient’s fibroblasts (Schuh et al. 2018a). CRISPR/Cas9 plasmids were delivered effectively into a triple-negative breast malignancy, using an antibody-conjugated tumor-targeted nanolipogel. The Lipocalin 2 gene knocking efficiency of 81 percent resulted in a 77 percent reduction in cancer growth. These investigations showed that tumor-targeted nanolipogel are a secure, precise, and efficient delivery vehicle for CRISPR-mediated genome editing with target specificity (Guo et al., 2019).
Introduction to mucopolysaccharidoses
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Hurler disease was originally classified by McKusick as mucopolysaccharidosis type I [1]. With the recognition of the enzyme defect in α-L-iduronidase and the fact that defective activity of the same enzyme was also the cause of the Scheie syndrome [8], the subclassifications IH for Hurler and IS for Scheie were employed. The classification of the mucopolysaccharidoses and a summary of their clinical biochemical characteristics are shown in Table 75.1. The seven types of mucopolysaccharidosis represent the deficiencies of eleven specific enzymes. Prenatal diagnosis was initially carried out in Hurler and Hunter diseases by measuring labeled sulphate incorporation in cultured amniocytes [10].
Biocatalytic Nanoreactors for Medical Purposes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Oscar González-Davis, Chauhan Kanchan, Rafael Vazquez-Duhalt
Mucopolysaccharidosis type I (MPS I) is a rare disease in which the body is missing or does not have enough of α-L-iduronidase needed to break down long chains of glycosaminoglycans. There are several other types of MPS, including MPS II or Hunter syndrome originated by the absence of iduronate-2-sulfatase; MPS III or Sanfilippo syndrome derived by low activity of N-acetylglucosaminidase; MPS IV or Morquio syndrome originated by the absence of galactose-6-sulfate sulfatase activity, and MPS VI derived from the absence of N-acetylgalactosamine-4-sulfatase. The ERT has been studied for most of MPS subtypes (Dornelles et al., 2017; Whiteman and Kimura, 2017; Gilkes and Heldermon, 2014; Tomatsu et al., 2015; Vairo et al., 2015).
The potential of gene therapy for mucopolysaccharidosis type I
Published in Expert Opinion on Orphan Drugs, 2020
Luisa Natalia Pimentel Vera, Guilherme Baldo
Mucopolysaccharidosis type I (MPS I-H) is an autosomal recessive disease caused by mutations in the IDUA gene localized at 4q16.3. This gene encodes the lysosomal hydrolase alpha-L-iduronidase (IDUA, EC 3.2.1.76), which is responsible for the hydrolysis of alpha-L iduronic acid residues of glycosaminoglycans (GAGs) Dermatan sulfate and Heparan sulfate [1,2]. This process is a fundamental step for the breakdown of these molecules in the lysosome and mutations in IDUA result in a deficient production or function of the enzyme. It causes progressive accumulation of GAGs within lysosomes, impairing its function [3]. As a result, loss of lysosomal function also involves secondary impairment of other pathways as autophagy and activation of inflammation. These alterations trigger a series of severe symptoms in patients, resulting in ocular, skeletal, visceral, and neurological manifestations, causing death at early ages [1,4,5].
Mucopolysaccharidosis Type I and Bilateral Optic Disc Edema
Published in Neuro-Ophthalmology, 2019
Sean M. Gratton, Thanuja Neerukonda
Mucopolysaccharidosis type I (MPS I or Hurler syndrome) is a multisystem genetic disorder caused by α-L-iduronidase (IDUA) deficiency, which leads to widespread accumulation of glycosaminoglycans triggering tissue damage and organ dysfunction. Symptoms mostly start in the first year of life and include upper airway obstruction, laryngeal and tracheal narrowing, hearing and visual deficits, skeletal deformities, organomegaly, abdominal herniae, and progressive neurological disease with severe cognitive delay.1 A variety of ocular manifestations have been described in Hurler Syndrome including decreased visual acuity and high hyperopia,2 abnormal corneal hysteresis,3 and optic nerve head swelling and optic atrophy.4 Other mucopolysaccharidoses have ocular manifestations as well including diffuse fine corneal deposits, pigmentary retinal degeneration, pseudopapilledema, and macular-edema.5 The authors present the case of an 11-year-old boy with Hurler Syndrome and optic disc edema related to ocular glycosaminoglycan deposition.
OCT imaging of macular cysts and treatment response with nepafenac in mucopolysaccharidosis type 1
Published in Ophthalmic Genetics, 2023
Aslıhan Yılmaz Çebi, Mustafa Hepokur
MPS I (Mucopolysaccharidosis Type I) is a lysosomal storage disorder characterized by a defect in the enzyme alpha-L-iduronidase. MPS I is inherited in an autosomal recessive way and has two phenotypes: the more severe Hurler phenotype and the milder Scheie phenotype.(1) Glycosaminoglycan (GAG) substrates heparan sulfate and dermatan sulfate accumulate gradually within lysosomes of different tissues.(2) Stromal corneal clouding, glaucoma, cataract, and pigmentary retinopathy are all possible ocular presentations.(3) Degeneration of Müller cells and retinal pigment epithelium (RPE) is thought to be involved in the pathophysiology of macular and retinal abnormalities in MPS I patients.(2)