Pathogenesis, emerging therapeutic targets and treatment in sialidosis
Year: 2015
Type: article
Abstract: INTRODUCTION: gene, encoding the lysosomal sialidase NEU1. Deficient enzyme activity results in impaired processing/degradation of sialo-glycoproteins, and accumulation of oversialylated metabolites. Sialidosis is considered an orphan disorder for which no therapy is currently available. AREAS COVERED: mutations so far identified; NEU1 requirement to complex with the protective protein/cathepsin A for stability and activation; and the pathogenic effects of NEU1 deficiency. Studies of the molecular mechanisms of pathogenesis in animal models uncovered basic cellular pathways downstream of NEU1 and its substrates, which may be implicated in more common adult (neurodegenerative) diseases. The development of a Phase I/II clinical trial for patients with galactosialidosis may prove suitable for sialidosis patients with the attenuated form of the disease. EXPERT OPINION: Recently, there has been a renewed interest in the development of therapies for orphan LSDs, like sialidosis. Given the small number of potentially eligible patients, the way to treat sialidosis would be through the coordinated effort of clinical centers, which provide diagnosis and care for these patients, and the basic research labs that work towards understanding the disease pathogenesis.
Source: Expert Opinion on Orphan Drugs
Authors: Alessandra D’Azzo, Eda Machado, Ida Annunziata
Institution: St. Jude Children's Research Hospital
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Excessive Lysosomal Exocytosis Triggers Pathogenic Mechanisms in Sialidosis Mice, Functional Roles And Mechanisms Of Snornas In Pre-rrna P, GM1 as apoptotic signal in neurodegenerative GM1-gangliosidosis, Functional/Structural Studies of Mammalian Neuraminidase, Gene Transfer for Galactosialidosis - Resub
OpenAlex ID: W2075095334