The efficacy of enzyme replacement therapy in early-onset Tay-Sachs disease mouse model

Tay-Sachs disease is devastating disorder for the affected individual and his/her family, and success in treatment has been limited because of poor access to the brain, the most affected tissue. Based on studies in mice, enzyme replacement therapy (ERT) is one of the promising approaches to treatment for this disease. Previously, ERT for TSD was tested in clinical trials through intraventricular delivery and injections into the spinal canal. However, no reduction of GM2 ganglioside accumulation was detected in patients due to the limited amount of the enzyme that was able to reach neural cells (von Specht et al, 1979). It has been reported only a small amount of Hex A activity is needed to ameliorate the disease phenotype (Mahuran, 1991). Even though ERT has proven to be an effective treatment in several other lysosomal storage disorders like Gaucher disease ERT is not feasible for Tay-Sachs disease (Baldo,2015) because recombinant Hex A cannot cross the blood-brain barrier (BBB) (von Specht et al, 1979). The recombinant enzyme may be directly administrated into brain via intracerebroventricular injection. Although ERT for lysosomal storage diseases generally requires frequent administration, it should be further investigated and developed for patients with TSD to ameliorate symptoms in the peripheral body such as muscle weakness, spasm, and paralysis (Matsuoka et al, 2011). New models and therapies are needed. We believe that if successful, our proposed ERT approach has the potential to be developed into an inexpensive approach to treatment Tay-Sachs disease and may open avenues to treatment for other lysosomal storage disorders affecting the central nervous system.