The Drug Discovery Lab, under the direction of Professor Varghese John, announced in the May 14, 2020 edition of UCLA Health news the publication in ACS Chemical Biology of their "... Discovery of a novel class of compounds that function as dual inhibitors of the enzymes neutral sphingomyelinase-2 (nSMase2) and acetylcholinesterase (AChE). Inhibition of these enzymes provides a unique strategy to suppress the propagation of tau pathology in the treatment of Alzheimer's disease (AD)." In the report, they describe the key structure-activity relationship elements that affect relative nSMase2 and/or AChE inhibitor effects and potency, as well as the identification of two compound analogs that suppress the release of tau-bearing exosomes in vitro and in vivo. Dr. John stated “Identification of these novel dual nSMase2/AChE inhibitors represents a new therapeutic approach to AD and has the potential to lead to the development of truly disease-modifying therapeutics." Read more in ACS Chemical Biology.
Dr. Mario Mendez, Professor-in-Residence of Neurology, Psychiatry and Biobehavioral Sciences at the Geffen School of Medicine, was featured in an October 23 UCLA Newsroom article about identifying distinct characteristics of dementia caused b brain injury could prevent misdiagnosis of Alzheimer's disease.
Dr. Sarah Kremen, Clinical Physician of Neurology, David Geffen School of Medicine at UCLA; Director of Clinical Trials programs at the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, and Principal Investigator for California’s Alzheimer’s Disease Centers (CADC) at UCLA, was interviewed on June 19, The Alzheimer’s Prevention Registry article about why primary care doctors should evaluate patients for memory and thinking skills.
Researchers at the Drug Discovery Lab (DDL) at the Mary S. Easton Center for Alzheimer's Disease Research at UCLA have recently reported that an experimental drug known as A03, previously developed to treat depression, was found to increase brain levels of an enzyme Sirtuin1, or SirT1, and improve memory after oral treatment in mice genetically modified to have a protein called ApoE4, the most common genetic risk factor for AD. Increasing the levels of SirT1 may delay the buildup of the toxic tau pathology and improve cognition in Alzheimer's. The DDL is conducting additional research on A03 to evaluate its potential for clinical testing in Alzheimer's disease. The lab is also developing similar compounds that might be more effective in increasing SirT1 levels. The study was funded by the National Institute of Health.
UCLA Newsroom Research Alert - December 20, 2018:
"Experimental Alzheimer’s drug boosts SirT1 levels and improves memory in mice."
Dr. Lin Jiang, Assistant Professor of Neurology at David Geffen School of Medicine at UCLA, was featured in an October 22 UCLA Newsroom article about him and his team members identified the plaque binding site of b-amyloid to its receptor by determining the three-dimensional structure. Knowledge of this interaction is a critical first step toward finding a drug to prevent the interaction between the toxic proteins and brain cells. Dr. Jiang and his team are using computer software to assist them in the drug selection process.