Page 29 - ebook

Improved Cell-Permeable Parkin Is A Potent Therapeutics For
Elimination Of β-Amyloid Fibril In Alzheimer’s Disease Dementia

SangsunYoon, JoonnoLee, SujeongKim, DongjaeMin, SeungwooLee, SojungSung, EunnaChung, and DaewoongJo
Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM
β-Amyloid (Aβ) and Tau Tangles are a pathological hallmark of It has been demonstrated that 1) iCP-Parkin was delivered into neurons
Alzheimer’s disease (AD) can cause dysfunction and death of neurons in localized in the deep brain, and 2) protected neurons by suppressing
brain, where pathogenesis of AD mainly happens. To deliver therapeutic accumulation of damaged pathological Aβ in hippocampus & cortex,
neuroprotective molecules into target neurons without direct injection, it consequently exerting reversible recovery of cognitive in Aβ-induced and
should be able to penetrate the blood-brain barrier (BBB). Improved cell- okadaic acid-induced AD animals. The goal of this study is to expand the
permeable Parkin (iCP-Parkin) has been developing by fusing Parkin with therapeutic scope of iCP-Parkin toward the AD field via a preclinical
a sequence-optimized hydrophobic cell-penetrating peptide, which was development.
maintained the E3 ubiquitin ligase activity of native Parkin.
METHODS
Fibril Amyloid-beta (fAβ, 4μg/head) and Okadaic acid (100 ng/head) were stereotaxically injected in the hippocampus of brain to generate AD animals.
After brain surgery, AD animals were treated with iCP-Parkin 100 mg/kg for 4 weeks. The efficacy of iCP-Parkin in AD animals was measured by
cognitive behavior test (Y-maze). AD animal was placed in the center of the Y-maze and was free to explore the arms for 8min. A spontaneous
alternation was defined as an entry into three different arms on consecutive choices. Another experiment, After IV injection of iCP-Parkin 100 mg/kg to
AD animals and prep the samples (brain, plasma), that was analyzed by LC-MS/MS at Covance (UK).
RESULTS

Figure 1. iCP-Parkin Recovers Cognitive Dysfunction & Figure 1. iCP-Parkin Recovers Cognitive Dysfunction &
Reduces Pathological Aβ Aggregates In fAβ-Induced AD Animals Reduces p-Tau Expression In Tauopathy Animals
A A

91%
B D
B C

94%
E
86%
133%
C

Scale Bar = 20 m
Student t-Test, * & # p<0.05, ** p<0.01 & ### p<0.001 Student t-Test, * p<0.05
Figure 3. aMTD-Mediated Brain Delivery Figure 4. iCP-Parkin Has Neuroprotective
Of Parkin Is Determined & Anti-Oxidative Effects In Neuronal Cells
A
A B

B C 78% 104%

CONCLUSION REFERENCES CONTACT INFORMATION
Chung et al. (2020) Science Advances, 6: eaba 1193
These results suggest that iCP-Parkin has Sangsun Yoon, Ph.D
Lim et al. (2013) Clinical Cancer Research, 19: 680-690
cytoprotective effect in neurons with a reduction Cellivery Therapeutics, Inc.
of Fibril Aβ & phospho-Tau. Through it will be Lim et al. (2013) Biomaterials, 34: 6261-6271 yoonss@cellivery.com
developed as a novel neuroprotective therapy Lim et al. (2012) Molecular Therapy, 20: 1540-1549
for dementia in AD Jo et al. (2005) Nature Medicine, 11: 892-898 +82-2-3151-8900
Jo et al. (2001) Nature Biotechnology, 19: 929-933 S4-1 신진과학자