Glucocerebrosidase (GCase), encoded by the gene GBA1, is a ubiquitous lysosomal enzyme that breaks down lipid substrates, glucosylceramide (GL-1) and glucosylsphingosine (Lyso-GL1), into glucose and ceramide. Loss-of-function mutations in GBA1 reduce GCase activity, resulting in lipid accumulation within lysosomes and subsequent lysosomal dysfunction.
Friedreich’s ataxia (FA) is an inherited neurodegenerative disorder caused by GAA repeat expansions in the FXN gene, which produces a mitochondrial protein vital for iron-sulfur cluster assembly and energy metabolism. Researchers at Solid Biosciences Inc. presented preclinical data supporting the first-in-human trial on SGT-212 gene therapy in FA models.
A therapeutic strategy based on alternative splicing of the MECP2 gene could restore protein levels in Rett syndrome, a neurological disorder caused by mutations in that gene. Scientists at Baylor College of Medicine have successfully tested this approach both in vitro in neurons from Rett patients that produce some functional protein, correcting the altered gene expression and improving neuronal functions, and in vivo in mice.
Researchers from University College London and collaborating institutions have recently published results from their study aiming to optimize gene therapy for CLN5 disease.
Hunter syndrome, also called mucopolysaccharidosis II, is an X-linked genetic lysosomal disorder caused by loss-of-function mutations in the IDS gene, encoding iduronate-2-sulfatase (I2S). I2S is a lysosomal enzyme responsible for the cleavage of glycosaminoglycans (GAGs), and its deficiency results in accumulation of GAGs leading to a multisystemic disorder.
Friedreich’s ataxia (FA), the most common form of hereditary ataxia, is an autosomal recessive neurodegenerative disorder affecting multiple organ systems, and causing cardiomyopathy, scoliosis, muscle weakness, speech impairment and other systemic issues.
A new method, based on gene editing with oligonucleotides and functional analyses, identifies which variants of DNA repair genes associated with Lynch syndrome are truly harmful and which are not. Scientists at The Netherlands Cancer Institute have developed this technique and classified these gene variants in both coding and noncoding regions, distinguishing those that are pathogenic from those that are benign.
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