Small Molecule TFEB Activators for Treating Alzheimer’s Disease

SK2016-121

SUMMARY OF INVENTION

Currently, there are no effective treatments for slowing the progression of Alzheimer’s Disease (AD).  Pathologically, the brains of Alzheimer’s Disease (AD) patients are characterized by the presence of extracellular amyloid plaques consisting of β-amyloid peptides (Aβ) and intracellular neurofibrillary tangles (NFT) composed of Tau protein.  Increasing evidence indicates that toxic Aβ and Tau aggregates accumulate as a result of impaired clearance.  Therefore, enhancing toxic protein clearance represents a promising treatment approach for AD. 

Transcription Factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy. TFEB has been shown to specifically clear toxic protein aggregates, such as Tau, as well as Aβ.  Therapeutic modulation of TFEB expression may present the unique and much sought-after opportunity to simultaneously address both Aβ and Tau pathology in AD. 

MSK investigators have conducted a high-throughput screen to identify small molecules that specifically promote TFEB-mediated clearance of Tau protein for treatment of AD, and identified several novel hits. Investigators are currently conducting a medicinal chemistry campaign at MSK to optimize these initial novel hits.

ADVANTAGES

  • Activators of TFEB could be a sought-after opportunity to address both Aβ and Tau to treat AD
  • Novel hits have been identified from an HTS screen
  • Investigator has set up in vitro and in vivo models to test lead compounds for efficacy, including memory paradigms to evaluate learning and memory function

MARKET OPPORTUNITIES

There is a high unmet need for effective therapies to slow the progression of Alzheimer’s Disease, with over 5 million people in the U.S., and 26 million worldwide, suffering from this condition. 

AREAS OF APPLICATION

Alzheimer’s Disease and other neurodegenerative diseases associated with the aggregation of Tau protein, including Frontotemporal Dementia

STAGE OF DEVELOPMENT

Preclinical

PATENT INFORMATION

U.S. Provisional Patent application filed in February, 2017

LEAD INVESTIGATOR

Yueming Li, PhD, Laboratory Head, Molecular Pharmacology Program, Memorial Sloan Kettering

CONTACT INFORMATION

Eileen Flowers, PhD

Licensing Manager
Tel: 646-888-1067
E-mail: flowerse@mskcc.org

Stage of Development

In vitro