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Mitochondria Delivery of FXN Ameliorates Abnormal Iron
Metabolism In FXN-Deficient Cells And Animal Models

Shinyoung Park, Jeongheon Choi, Hoegon Ryu, Hakyoung Park, Eunna Chung and Daewoong Jo
Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM
Friedreich’s ataxia (FRDA) is a rare monogenic disease with To replenish insufficient mitochondria FXN in FRDA-mimicked
neurodegeneration and cardiomyopathy. FRDA is caused by a deficiency of cells and animals, Cell-Permeable FXN (CP-FXN) recombinant
the mitochondrial protein called frataxin (FXN), which is critical for ion-sulfur protein has been developed by fusing advanced macromolecule
cluster (ISC) biosynthesis and regulation of iron metabolism. transduction domain (aMTD) to human mature FXN.

METHODS
In cell model, the biological activity and the intracellular & mitochondrial localization following CP-FXN treatment were evaluated by ATP-Glo
assay, flow cytometry and immuno-based assay. CP-FXN has been treated into cardiac FXN KO mice with various administration routes (IP & IV),
frequencies and doses (30 & 50 mg/kg). Then, the molecular and histological changes in the cardiac tissue were investigated. Brain- KO mice
were administered with a single intramuscular (IM) injection of 30 mg/kg CP-FXN.

RESULTS
Figure 4. Intravenous (IV) Administration of Figure 6. Low & High Frequency Of CP-FXN Have
Figure 1. CP-FXN Is Co-Localized CP-FXN Is More Effective Route To Expand Life Similar Effect On Body Weight Change
With Mitochondria Span In Cardiac FXN KO Animals In Cardiac FXN KO Animals
A B
Protocol Optimization: Route Protocol Optimization: Frequency
(IP & IV, 50 mg/kg, 3 times/week) (IV, 100 mg/kg, 3/W & 7/W)

Figure 2. CP-FXN Is Intracellularly Distributed
In Brain and Heart of Normal Mouse
A
700%
Histological Analysis Aconitase Activity Histological Analysis
* p < 0.05 vs. FXN KO+Diluent
800%

B C
100 µm
100 µm
Figure 5. High Dose Of CP-FXN Is More Effective
To Prevent Body Weight Loss In Cardiac
FXN KO Animals Figure 7. CP-FXN Restores Aconitase &
SDH Activity In Brain-FXN KO Animals
Protocol Optimization: Dose
Figure 3. CP-FXN Restores Aconitase & (IV, 30 & 100 mg/kg, 3 times/week)
SDH Activity In FXN-Knockdowned Cells   Animal: Brain FXN KO (PV-Cre), 7 w, Male
Treatment: 30 mg/kg
 Route: IM injection
A * p < 0.05,  After 4 H single injection
* 110% * * 87% SDH Activity Aconitase Activity
* (Mitochondria of Cerebellum) (Mitochondria of Brain)

Aconitase Activity Iron Accumulation
B * p < 0.05,
* * * * * p < 0.05 vs. FXN KO+Diluent
100% 51% 55%
100 µm
Student t-test
* p < 0.05, *** p < 0.001
Error Bar: SE
100 µm
CONCLUSION REFERENCES CONTACT INFORMATION
Chung et al. (2020) Science Advances, 6: eaba 1193
These data suggest that CP-FXN with Shinyoung Park, Cellivery R&D Institute
superior intracellular & mitochondria Lim et al. (2013) Clinical Cancer Research, 19: 680-690
targeting delivery may provide a therapeutic Lim et al. (2013) Biomaterials, 34: 6261-6271 Cellivery Therapiutics, Inc.
potential for FRDA treatment by improving Lim et al. (2012) Molecular Therapy, 20: 1540-1549 parksy@cellivery.com
iron homeostasis in the heart and brain. Jo et al. (2005) Nature Medicine, 11: 892-898 +82-2-3151-8900
Jo et al. (2001) Nature Biotechnology, 19: 929-933