Study Reports Link Between Alzheimer’s Cellular Abnormalities

Neurogenetics, Inc. has reported that a study published in the September issue of Neuron links a new mechanism-based therapeutic approach, licensed by the Company from Massachusetts General Hospital (MGH), to Alzheimer’s disease (AD). Researchers from the MGH Genetics and Aging Unit report that they have discovered a key link between two cellular abnormalities associated with the disease — mutations in genes encoding presenilin proteins and an altered handling of calcium inside cells.

While many cellular pathways can affect the flow of calcium into and out of a cell, the results from MGH tie one specific pathway, capacitative calcium entry (CCE), to the production of amyloid-beta42 (A-beta42). A-beta42 is a sticky protein fragment deposited in plaques found in the brains of people with AD. In normal cells, calcium is stored in a cellular compartment called the endoplasmic reticulum (ER), that is refilled through the CCE process.

The authors’ findings indicate that presenilin mutations known to be associated with the inherited form of early-onset AD inhibit the CCE process, resulting in increased production of A-beta42.

has exclusively licensed from MGH the approach of treating Alzheimer’s by modulating CCE. Kenneth A. Stauderman, Ph.D., Project Leader and Executive Director, Cell Biology and Physiology at Neurogenetics, commented,

“Based on these findings, has developed specific, cell-based assays to identify drugs that modulate the entry of calcium through the CCE pathway.

Targeting CCE for drug discovery represents a unique mechanistic approach for selectively inhibiting A-beta42 production.”

Neurogenetics, Inc., founded in April 2000, is a San Diego-based emerging biopharmaceutical company focused on the development of novel small molecule therapeutics for Alzheimer’s disease (AD).