Estrogen is known to be a negative regulator of KNDy neurons, which act upstream of heat dissipation effectors. As estrogen levels fall in peri-menopausal women, the absence of estrogen negative feedback causes KNDy neurons to become hypertrophic and hyperactive. Hyperactivity of KNDy neurons is believed to initiate the process that causes VMS.
By inhibiting NK3R signaling on KNDy neurons, MLE4901 is intended to reduce KNDy neuron hyperactivity, thereby restoring normal functioning of heat dissipation effectors and resolving the dysregulation that results in VMS. The NK3R is also believed to be a key regulator of heat dissipating neurons, which we believe further supports the potential of MLE4901 to treat VMS.