Impact of Anti-CCL3 FANA Oligonucleotide in T10 contusion Spinal Cord Injury using female mice on locomotor function, and inflammation

DOI:10.34945/F55305

DATASET CITATION

Pelisch N., Rosas Almanza J., Xiong S., Stehlik K. E., Aperi B. V., Kroner-Milsch A. (2023) Impact of Anti-CCL3 FANA Oligonucleotide in T10 contusion Spinal Cord Injury using female mice on locomotor function, and inflammation. Open Data Commons for Spinal Cord Injury. ODC-SCI:941 http://doi.org/10.34945/F55305

ABSTRACT

STUDY PURPOSE: Secondary damage after spinal cord injury (SCI) occurs because of a sequence of events after the initial injury, including exacerbated inflammation that contributes to increased lesion size and poor locomotor recovery. Thus, mitigating secondary damage is critical to preserve neural tissue and improve neurologic outcome. In this work, we examined the therapeutic potential of a novel antisense oligonucleotide (ASO) with special chemical modifications [2'-deoxy-2-fluoro-D-arabinonucleic acid (FANA) ASO] for specifically inhibiting an inflammatory molecule in the injured spinal cord. The chemokine CCL3 plays a complex role in the activation and attraction of immune cells and is upregulated in the injured tissue after SCI.

DATA COLLECTED: We used specific FANA ASO to inhibit CCL3 in a contusive mouse model of murine SCI (C57BL/6, female, Charles River). These chemically modified RNA inhibitors penetrate cell membranes without the need for transfection. Our results show that, after intrathecal injection, FANA ASO molecules targeting the chemokine CCL3 penetrate the spinal cord lesion site and suppress the expression of CCL3 transcripts (p-value < 0.001). Furthermore, they reduce other proinflammatory cytokines such as tumor necrosis factor (TNF, p-value < 0.001) and interleukin (IL)-1beta after SCI (p-value 0.0034).

CONCLUSIONS: In summary, we demonstrate for the first time the potential of FANA ASO molecules to penetrate the spinal cord lesion site to specifically inhibit CCL3, reducing proinflammatory cytokines and improve functional recovery after SCI. This novel approach may be used in new treatment strategies for SCI and other pathologic conditions of the CNS.

KEYWORDS

CCL3; FANA ASO; inflammation; novel RNA inhibitor; secondary damage; spinal cord injury.

PROVENANCE / ORIGINATING PUBLICATIONS

• Use of a Self-Delivering Anti-CCL3 FANA Oligonucleotide as an Innovative Approach to Target Inflammation after Spinal Cord Injury.. doi:10.1523/ENEURO.0338-20.2021.

RELEVANT LINKS

NOTES

DATASET INFO

Contact: Kroner-Milsch Antje (akroner@mcw.edu)

Lab: Kroner

ODC-SCI Accession:941

Records in Dataset: 102

Fields per Record: 54

Last updated: 2023-10-04

Date published: 2023-10-04

Downloads: 1

Files: 2

LICENSE

Creative Commons Attribution License (CC-BY 4.0)

FUNDING AND ACKNOWLEDGEMENTS

Department of Neurosurgery (Startup Funding) N/A

CONTRIBUTORS

Pelisch, Nicolas

MCW

Rosas Almanza, Jose

MCW

Xiong, Shuana

MCW

Stehlik, Kyle E E.

MCW

Aperi, Brandy V.

MCW

Kroner-Milsch, Antje [ORCID:0000-0001-5897-9774]

MCW