Embryonic Stem Cell-derived A9 Dopaminergic Neuronal Precursor Cells
|Basic Research||Non-clinical||Phase 1||Phase 2||Phase 3||Approval|
Nonclinical trial complete scheduled to apply for IND
The differentiation into A9 dopaminergic neuron precursor cells (A9-DPC) was confirmed by high expression of En1, FoxA2, and Lmx1A, which are specifically expressed in A9-DPC in the differentiated cells.
EN1+/FOXA2+ /LMX1A+ Cell
Dopamine concentration was measurement by inducing differentiation into dopaminergic neurons with TED-A9. As a result of checking dopamine concentrations in differentiation cell cultured medium (Conditioned media), differentiation cell cultured medium stimulated by potassium chloride(KCl), and differentiation cell lysate (Lysate), dopamine was detected in all conditions. Through this, it was confirmed that the differentiated dopaminergic neurons on TED-A9 have functionality.
In the efficacy test on rats, a Parkinson’s disease model was created by using 6-OHDA (6-hydroxydopamine) to kill dopaminergic neurons in one side of their brains. Thereafter, the model was treated with amphetamine to induce asymmetric rotation and the effect of reducing the asymmetric rotation rate due to cell was measured. As a result, the gradual decrease in the number of asymmetric rotations was confirmed over time after TED-A9 transplant.
In order to reproduce Parkinson's disease in humans, an animal model was prepared with marmoset monkeys using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the control group, the severity was maintained whereas in the group with TED-A9 transplant, the severity decreased and recovery to an almost normal state was observed after 200 days.