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http://dx.doi.org/10.4103/aian.aian_577_21 | DOI Listing |
Nat Med
August 2025
Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
The dual rAAVrh8-HEXA and rAAVrh8-HEXB vector can restore central nervous system hexosaminidase (Hex) enzyme activity, decrease GM2 levels in cerebrospinal fluid and rescue phenotypic consequences of GM2 gangliosidosis, Tay-Sachs and Sandhoff diseases in animal models following simultaneous bi-thalamic (BiT) injections. Following up on an n = 2 expanded access trial, we initiated a phase 1/2, single-dose, dose-escalation of combined BiT, intra-cisterna magna and intrathecal infusion in children with Tay-Sachs and Sandhoff diseases (six infantile, three juvenile). The BiT injection volume and vector dose were doubled between four cohorts, with the lowest dose matching the earlier expanded access trial.
View Article and Find Full Text PDFNeurol Int
June 2025
Experimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, School of Health Sciences, University of Jaén, E23071 Jaén, Spain.
Tay-Sachs disease (TSD) is a rare and severe neurodegenerative disorder inherited in an autosomal recessive manner. It is caused by a deficiency of the enzyme hexosaminidase A, which is responsible for the degradation of GM2 gangliosides-lipids that accumulate in the nerve cells of the central nervous system. The inability to break down these lipids leads to their progressive accumulation, resulting in irreversible brain damage.
View Article and Find Full Text PDFMol Genet Metab Rep
June 2025
Demiroglu Bilim University Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey.
GM2 activator deficiency (AB variant of GM2 gangliosidosis) is an ultra-rare autosomal recessive lysosomal storage disorder caused by pathogenic GM2A mutations. The loss of a functional GM2 activator protein disrupts GM2 ganglioside degradation, leading to progressive neurodegeneration. Although it shares clinical features with Tay-Sachs disease, GM2 activator deficiency remains a genetically and biochemically distinct disorder, with limited genotype-phenotype correlation due to the small number of reported cases.
View Article and Find Full Text PDFJ Spec Educ Technol
March 2024
Center for Education in Health Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois.