Page 29 - Q. Neuroscience

Aggregation Of α-Synuclein In Parkinson’s Disease: Delivery Of Parkin To
Brain Prevents Dopaminergic Neuronal Loss And Improves Behavior

Sangsun Yoon, Yunseo Hwang, Dongjae Min, Jongseok Lee, Hyunwoo Kang, Joohyun Pi, Youngsil Choi, and Daewoong Jo
Neurodegenerative Disease Drug Development Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM
Parkinson's disease (PD) is a neurodegenerative disorder, which is This study describes that a protein-based therapy of iCP-Parkin
pathologically characterized by dopaminergic neuronal loss and ameliorates PD induced by aggregated α-Synuclein, suggesting
formation of Lewy bodies in substantia nigra (SN) and striatum. common features in underlying pathophysiology and a potential
Improved cell-permeable Parkin (iCP-Parkin) has been developing therapeutic effect to treat PD even after the onset of motor
by fusing Parkin with a sequence-optimized hydrophobic cell- symptoms.
penetrating peptide, that was maintained the E3 ubiquitin ligase
activity of native Parkin.
METHODS
AAV-α-Synuclein-induced PD mice were stereotaxically injected with the human WT α-synuclein AAV/DJ vector into the substantia nigra in brain.
After brain surgery, mice were treated with iCP-Parkin for 4 weeks. The efficacy of iCP-Parkin in PD mice was measured by behavior test.

RESULTS

Figure 1. iCP-Parkin recovered motor function Figure 2. iCP-Parkin recovered TH expression AAV-α-Synuclein-
in AAV-α-Synuclein-induced mouse model induced in whole brain

A B A B

Behavior Test (Rota-Rod) Behavior Test (Pole)

Figure 3. iCP-Parkin recovered TH expression AAV-α-Synuclein-
induced in substantia nigra and striatum

Substantia Nigra Striatum

Figure 4. iCP-Parkin rescues damaged dopaminergic neuron Figure 5. iCP-Parkin removes α-Synuclein
in substantia nigra aggregates in substantia nigra

A C

B

D

CONCLUSION REFERENCES Contact information
Chung et al. (2020) Science Advances, 6: eaba 1193
These results suggest that iCP-Parkin has Minyong Jung
cytoprotective effect in dopaminergic neuronal Lim et al. (2013) Clinical Cancer Research, 19: 680-690 New Drug & Business Development
cells with a reduction of aggregated α-Synuclein, Lim et al. (2013) Biomaterials, 34: 6261-6271 Cellivery Therapeutics, Inc.
offering a novel potential therapeutic opportunity Lim et al. (2012) Molecular Therapy, 20: 1540-1549 jungmy@cellivery.com
in PD treatment. Jo et al. (2005) Nature Medicine, 11: 892-898
Jo et al. (2001) Nature Biotechnology, 19: 929-933 +82-2-3151-8900