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Use of Repurposed Compounds for the Treatment of Alzheimer’s Disease

Summary
The National Institute on Aging (NIA) seeks research licensees and/or co-development partners under a Cooperative Research and Development Agreement (CRADA) to advance preclinical and clinical development of repurposed compounds to treat Alzheimer’s disease.
NIH Reference Number
E-207-2021
Product Type
Keywords
  • Alzheimer’s Disease, Apolipoprotein-E, APOE, STAT3, YES1, FYN, Neuroinflammation, Tau Phosphorylation, Aβ, National Institute on Aging, NIA, Thambisetty
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

There are no effective treatments for Alzheimer’s disease (AD), a progressive brain disease that slowly destroys a person’s memory, cognitive skills and ability to carry out the simplest tasks. AD affects more than 5 million individuals in the United States and ranks as the sixth leading cause of death. The ε4 allele of the apolipoprotein-E (APOE) gene is the strongest genetic risk factor for sporadic or late-onset AD. Heterozygous carriers of the ε4 allele are at three-to-four times greater risk; homozygous carriers are at ten times greater risk. In fact, APOE ε4 carriers accumulate AD neuropathology early in adulthood with earlier age onset of AD compared with ε4 non-carriers.

Researchers at the National Institute on Aging (NIA) identified a brain proteomic signature comprised of 25 proteins that may drive the risk for developing AD in young APOE ε4 carriers. NIA researchers further identified compounds that target proteins in this AD proteomic signature and rescue molecular abnormalities associated with AD. Specifically, the STAT3 inhibitors TTI-101 and hydroxychloroquine rescued three specific AD phenotypes in cell culture-based phenotypic screens: (1) lipopolysaccharide (LPS)-induced neuroinflammation; (2) tau phosphorylation; and (3) Aβ secretion/Aβ clearance. Dasatinib, a YES1/FYN inhibitor, lowered tau phosphorylation. These findings reveal that TT1-101, hydroxychloroquine and Dasatinib – among other approved and experimental drugs – may be repurposed to treat AD.

The NIA seeks co-development partners and/or licensees for the further pre-clinical and clinical development of TTI-101, hydroxychloroquine, and Dasatinib to treat Alzheimer’s disease.

Potential Commercial Applications
  • A therapeutic for patients with Alzheimer’s disease
  • A therapeutic for APOE ε4 carriers with Alzheimer’s disease 
  • A therapeutic for APOE ε4 carriers with early signs of Alzheimer’s disease

 

Competitive Advantages
  • Prevent the development and progression of Alzheimer’s disease in high-risk APOE ε4 carriers
  • Expedited approval process due in part to pre-existing safety data for repurposed drugs

 

Inventor(s)

Madhav Thambisetty MD PhD (NIA), Myriam Gorospe PhD (NIA), Carlos Anerillas-Aljama Ph.D (NIA)

Development Stage
Publications

Roberts JA, et al. A brain proteomic signature of incipient Alzheimer’s disease in young APOE ε4 carriers identifies novel drug targets.  [PMID 34757788]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 63/253,992 , Filed 08 Oct 2021
Therapeutic Area
Updated
Wednesday, February 23, 2022