Advantages
- Oral administration of the molecule decreases tau aggregates in the brain of tauopathy model mice.
- Screening tool using originally developed tauopathy model cell for drug candidate degrading tau aggregates
Technology Overview & Background
Accumulation of ubiquitinated protein aggregates is a common pathological feature in neurodegenerative diseases such as Alzheimer‘s disease (AD), Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB), and Frontotemporal lobar degeneration (FTLD). The autophagy-lysosome pathway (ALP) plays an important role in the pathogenesis of these diseases. Recent studies have demonstrated that ubiquitinated-protein aggregates can be selectively recognized by autophagy receptors and then be degraded by ALP, a process termed aggrephagy.
The researchers focused on the p62/SQSTM1-mediated aggrephagy. p62/SQSTM1 plays a crucial role in this mechanism as a key autophagy receptor in aggrephagy. During aggrephagy, p62 requires phosphorylation at S403 and stabilizes the interaction between p62 and polyubiquitin chains. The phosphorylation facilitates autophagosomal engulfment of ubiquitinated-protein aggregates. They also demonstrated that artificial activation of p62 mediated aggrephagy by expressing the mutant p62 (S403E) can suppress aggregate formation in mouse brain. They hyptohesized that small molecules that induce p62 expression and its S403-phosphorylation are expected to be drug candidates for neurodegenerative diseases.
The researchers screened small molecules that reduce fibrillar tau aggregates in a cultured cell model of tauopathy and found that ADI-29 inhibited phosphorylated tau accumulation and hippocampal atrophy in a mouse model of tauopathy (PS19) after 7 months of oral administration. These results suggest that ADI-29 is a good candidate for the development of drugs for dementia and other neurodegenerative diseases.
Patent
- Patent filed, not yet published
Principal Investigator & Academic Institution
Dr. Gen Matsumoto (Department of Histology and cell biology, Nagasaki University School of Medicine)
Development Stages & Plans
- Current stage：Oral administration of newly synthesized molecule (ADI-29) reduces phospho-Tau accumulation and hippocampal atrophy in PS19 tauopathy model mice.
- Next Step：We can set up a meeting with the PI to discuss collaboration or R&D. If there are any interest in new compounds screening using researcher’s screening tool, they can discuss the collaboration.
Expectations
TECH MANAGE CORP. is looking for a pharmaceutical company/start-up that is interested in licensing this invention for commercialization on behalf of Nagasaki University. We can also arrange a meeting with the PI of this invention. Please feel free to contact us with any requests you may have.
Project No. TT-04683