Technologies

Unmet Need
Alzheimer’s disease (AD) is the most common form of dementia, affecting approximately 5.7 million people in the United States in 2018. Yet, no cure exists for AD, and AD therapeutics presently on the market fail to treat the disease’s underlying causes. Recent studies in mice reveal that exosomes released from glial cells contribute to the propagation of tau, which are a hallmark of AD. Neutral sphingomyelinase 2 (nSMase2), which is critically involved in exosome synthesis, achieves this in part through its production of ceramide, a lipid that is elevated post-mortem in human AD. Further, pharmacological inhibition or genetic deletion of nSMase2 significantly has been shown to decrease tau propagation and improve cognition. Taken together, these provide a compelling rationale for the development of nSMas2 inhibitors as AD therapeutics. However, current inhibitors to nSMase2 have low potency, poor solubility and limited brain penetration, thereby limiting their therapeutic potential.

Technology Overview
JHU researchers have identified an inhibitor of human nSMase2, MS882, with nanomolar potency.