Page 23 - Q. Neuroscience

Replenishing Parkin Protects Neurons And Recovers Motor Function
From Neurotoxin (6-OHDA)-Mediated Cellular Stress
Younseo Hwang, Youngjin Seo, Eunna Chung, Junghwan Jo, Seungwoo Lee, Soyoung Park and Daewoong Jo
Drug Development Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea.

BACKGROUND AIM
Parkinson’s disease (PD) is a neurodegenerative disorder that iCP-Parkin, which is called improved Cell-Permeable (iCP) Parkin, is
causes abnormal movement due to the selective loss of able to be delivered intracellularly into deep brain by penetrating
dopaminergic neurons in brain. Parkin is an E3 ubiquitin ligase that blood-brain barrier (BBB). iCP-Parkin has therapeutic effects in
plays a critical role in the ubiquitination process to fix damaged various PD animal models by utilizing its capabilities of BBB
mitochondria. penetration and cytoprotective activity.

METHODS
C57BL/6 mice (9-13 weeks male) were anesthetized by a 1:1 mixture of Zoletil:Rumpun diluted 1:10 in saline; positioned onto a stereotaxic
apparatus and injected with 4 µg 6-OHDA dissolved in 0.8 µL of 0.01% ascorbic acid at a rate of 0.2 µL/min into the medial forebrain bundle
(MFB) at the following coordinates (relative to bregma): anterior-posterior (AP) = -1.2 mm, medial-lateral (ML) = -1.2 mm and dorsal-ventral (DV)
= -4.75 mm (from the dura) with a flat skull position. Control mice were injected with 0.01% ascorbic acid solution alone.
RESULTS

Figure 3. iCP-Parkin Recovered Motor Function
Figure 1. iCP-Parkin Shows High Solubility/Yield & Homogeneity
In 6-OHDA-Induced Mouse Model
A B

Figure 2. iCP-Parkin Shows High Cell-Permeability & Deep Tissues Transfer Figure 4. iCP-Parkin Recovered Motor Function
In 6-OHDA-Induced Rat Model
A B

B

Figure 5. iCP-Parkin Enhances TH Expression & Recovers Figure 6. iCP-Parkin Enhance TH Expression & Recovers
Motor Function in 6-OHDA-Induced PD Mouse Model Motor Function in 6-OHDA-Induced PD Rat Model
A C A B

B C

CONCLUSION REFERENCES Contact information
iCP-Parkin dose-dependently recovers the Chung et al. (2020) Science Advances, 6: eaba 1193 Minyong Jung
behavior defect significantly and promotes TH Lim et al. (2013) Clinical Cancer Research, 19: 680-690 New Drug & Business Development
expression in 6-OHDA-induced animal models, Lim et al. (2013) Biomaterials, 34: 6261-6271
by utilizing its E3 ubiquitin ligase activity. In Cellivery Therapeutics, Inc.
conclusion, based on these data, iCP-Parkin Lim et al. (2012) Molecular Therapy, 20: 1540-1549 jungmy@cellivery.com
may have a great therapeutic potential as a Jo et al. (2005) Nature Medicine, 11: 892-898
PD-modifying agent. +82-2-3151-8900
Jo et al. (2001) Nature Biotechnology, 19: 929-933