Tay-Sachs Disease
Tay-Sachs disease causes progressive neurodegeneration through toxic GM2 ganglioside accumulation in neurons, leading to irreversible synaptic dysfunction, axonal degeneration, and ultimately widespread neuronal loss in the central nervous system. At Protheragen, we are committed to advancing the understanding and management of Tay-Sachs disease through cutting-edge therapeutic development and disease modeling services.
Overview of Tay-Sachs Disease
Tay-Sachs disease is a fatal autosomal recessive lysosomal storage disorder caused by deficient β-hexosaminidase A (HexA) enzyme activity, leading to progressive GM2 ganglioside accumulation in neurons. First described in 1881 by Warren Tay and Bernard Sachs, Tay-Sachs disease manifests in three forms:
| Form | Onset Age | Disease Progression | HexA Activity | Genetic Profile |
| Infantile (Acute) | 3-6 months | Rapid (death by age 4) | <0.1% of normal | Severe loss-of-function mutations |
| Juvenile (Subacute) | 2-10 years | Moderate (death in teens) | 0.1-2% of normal | Missense/milder mutations |
| Late-onset (Chronic) | Adolescence to adulthood | Slow (decades-long course) | 2-10% of normal | Hypomorphic mutations |
Pathogenesis of Tay-Sachs Disease
Tay-Sachs disease is caused by mutations in the HEXA gene leading to β-hexosaminidase A deficiency, which results in toxic accumulation of GM2 ganglioside in neuronal lysosomes. This lysosomal storage disrupts cellular function, triggers secondary glycolipid buildup, and activates apoptotic pathways, ultimately causing progressive neurodegeneration whose severity correlates with residual enzyme activity.
Fig.1 Pathological mechanism of Tay-Sachs disease. (Solovyeva V V, et al., 2018)
Therapeutic Development for Tay-Sachs Disease
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| AXO-AAV-GM2 | Intrathecal AAV9-mediated gene therapy delivering functional HEXA gene | CNS neurons | NCT04669535 | Phase I/II |
| Venglustat | Glucosylceramide synthase inhibitor (substrate reduction therapy) | GM2 ganglioside production pathway | NCT04221451 | Phase II/III |
| IB1001 | Recombinant human hexosaminidase A enzyme replacement therapy (ERT) | Lysosomal GM2 ganglioside | NCT03759665 | Phase II |
| Pyrimethamine | Pharmacological chaperone stabilizing mutant HexA enzyme | Misfolded β-hexosaminidase A protein | NCT01102686 | Phase I/II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
At Protheragen, we focus on preclinical research in Tay-Sachs disease, providing comprehensive solutions from biomarker identification to development of CNS targeted therapeutics. Our expertise covers disease modeling, including patient-derived iPSCs, genetically engineered models, and advanced blood-brain barrier (BBB) models for evaluating drug penetration and neuroprotective efficacy. We provide partners with target validation, lead compound optimization, and comprehensive preclinical research services.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- HEXA Knockout Model: Disrupts β-hexosaminidase A (HEXA) activity, causing GM2 ganglioside accumulation and mild neurodegeneration.
- HEXB Knockout Model: Lacks both HEXA and HEXB activity, leading to severe Sandhoff-like pathology with rapid neurodegeneration and early lethality.
Protheragen takes pride in offering comprehensive preclinical research services for Tay-Sachs disease using advanced disease models. These services encompass various aspects of drug research, including pharmacodynamics (PD), pharmacokinetics (PK), and safety evaluations, ensuring a holistic approach towards drug development in this challenging medical area. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Solovyeva V V, Shaimardanova A A, Chulpanova D S, et al. New approaches to Tay-Sachs disease therapy[J]. Frontiers in physiology, 2018, 9: 1663.