Dr. Beth Stutzmann (NeuroLucent CSO & Assoc. Prof. RFUMS) has uncovered important disease biology that helps explain the cause of synaptic dysfunction in neurons leading to Alzheimer’s disease (AD). Her lab at RFUMS has generated substantial evidence that links the elevated cytoplasmic Ca2+ levels that occur in AD to the overexpression/overstimulation of a critical intracellular Ca2+ transporter, RyR2, located in the endoplasmic reticulum membrane.
The RFUMS team has achieved a critical milestone with the identification of a novel series of compounds that normalize RyR2 function and restore normal Ca2+ homeostasis in AD neurons. The therapeutic potential of prototype compounds has been validated in AD mouse models and human neurons from AD patients, in which their ability to normalize Ca2+ levels and decrease AD biomarkers has been demonstrated.
NeuroLucent’s RyR2 modulators provide a unique opportunity to explore ‘upstream’ targets in this disease pathway for more effective therapeutic intervention—which is now widely viewed as critical for success in treating the cognitive decline associated with AD. NeuroLucent compounds have the potential to maintain synaptic health and keep memory function intact. If this therapeutic profile is confirmed, a NeuroLucent drug could be used for all stages of the disease, with particular utility in early- to mid-stage AD patients for slowing or preventing cognitive decline.