Advantage and Core Benefit
- Therapeutic agent using short-chain peptides that inhibit synuclein aggregate formation and disaggregation
Background and Technology
One of the pathogenic mechanisms of Parkinson’s disease is thought to be the accumulation of alpha-synuclein (α-Syn) in neurons and the formation of aggregates. In order to elucidate the pathogenic mechanism of Parkinson’s disease, animal models in which forced expression of α-Syn, mutant proteins, or aggregates are administered into the brain have been proposed, and therapeutic drugs are being developed.
In this study, the inventors focused on the aggregation of α-Syn and identified fragment peptides (Syn-FPs) that serve as aggregation nuclei. Intracerebroventricular administration of these Syn-FPs to mice resulted in Parkinson’s disease-like symptoms, such as decreased cognitive and motor functions. In addition, we identified two peptides derived from human protein molecules (LYZA-3 and YS-RD11) that inhibit the aggregation of α-Syn from the original peptide library and administered them to a Syn-FPs-treated model with PD-like symptoms, which improved cognitive and motor function decline. It has also been suggested that YS-RD11 may inhibit the aggregation of amyloid-β and is expected to be developed as a therapeutic agent for Alzheimer’s disease.
- In the Syn-FPs group, the time spent in the Rota-Rod test was decreased, indicating motor dysfunction, while the time spent in the YS-11 and LYZA-3 peptide groups was similar to that in the Saline group.
- In the Y-maze test (D74), there was a decrease in Alteration Rate, an index of cognitive function, in the Syn FPs group compared to the Saline group, but Alteration Rate was higher in the YS-11 and LYZA-3 groups.
Patent No. Pending in Japan (Unpublished)
Toshifumi Akizawa (Kochi University)
The inventors plan to conduct histological evaluation of the pathology of the PD-like animal model, further demonstration of the animal model by increasing the number of animals, and intranasal administration. We are open to collaborations with biotech companies with DDS technology to reach the brain, CROs and animal models to establish animal models, and can disclose the sequence of YS-RD11 and LYZA-3 peptides and the amino acid sequence of the origin and Syn-FPs under NDA. We can also provide peptides for evaluation studies under a paid MTA.
Product No. WL-03994