149: FAM19A5 as a Therapeutic Target for Restores Neuron-Satellite Gilal Cells Interaction in Pain.

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, , , , , , , , , , Electrophysiology, Drug development, Behavioral studies

Background and Aims: Proper neuronal function depends on tightly regulated interactions between neurons and surrounding other cells. Disruption of these interactions contribute to neurological disorders. In this study, we suggest the neuropeptide FAM19A5 as a critical modulator of interaction between cell to cell. Recently, it has been reported that FAM19A5 regulates synaptic adhesion between a leucine-rich repeat-containing molecule and a receptor protein tyrosine phosphatase, thereby leading to neurological disorders. We hypothesized that a similar FAM19A5-medicated mechanism also occurs between neurons-satellite glial cells (SGCs) within the dorsal root ganglion (DRG) and that this disruption may be associated with neuropathic pain.

Methods: * Pain Test: The chronic constriction injury (CCI), complete Freund’s adjuvant (CFA), and chemotherapy-induced peripheral neuropathy (CIPN) were generated. Following model induction, nociceptive behaviors were evaluated. Mechanical sensitivity was assessed using the von_Frey test, while thermal sensitivity was measured using the Hargreaves test and the acetone evaporation test
* Transmission Electron Microscope: Imaging was carried out using a Hitachi (H-7650) electron microscope.
* Calcium Imaging and Electrophysiology: Fura-2-loaded neurons were recorded about fluorescence intensity ratios at excitation wavelengths of 340 and 380 nm. Whole-cell patch-clamp was also performed on cultured single neuronal cells and were performed in the same environment as calcium imaging.

Results: In vivo delivery of an anti-FAM19A5 antibody via viral vector enable sustained neutralization of FAM19A5 in the DRG. Clearance of FAM19A5 restored the structure of neuron-SGC contacts that were damaged under neuropathy. We confirmed by transmission electron microscopy that anti-FAM19A5 restored the morphological normalization of cells, which are damaged in neuropathy. Furthermore, it was accompanied by significant therapeutic effects across multiple neuropathic pain models. FAM19A5 clearance through gene therapy showed an alleviation of signal transmission in the functional aspect of neurons. By examining this from electrophysiological techniques, we confirmed that FAM19A5 clearance can lead to effective analgesia.

Conclusions: These findings demonstrate that maintaining a normal microenvironment of DRG is essential for normal nociceptive processing. FAM19A5 functions as a key regulator of neuron-SGC structural interactions in peripheral neuropathic states. Neutralization of anti-FAM19A5 reverses pathological remodeling and reduces pain behaviors. Therefore, therapeutic clearance of FAM19A5 represents a promising antibody-based strategy for restoring neuron-SGC homeostasis and treatment of peripheral neuropathic pain.

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Presenting Author: Chaeeun Kim
Submitting Author: Chaeeun Kim

Senior Author: Sun Wook Hwang

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Chaeeun Kim - Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea
• Solji Kim - Neuracle Genetics Inc, Seoul, 02841, Republic of Korea
• Jaewoo Lee - Neuracle Genetics Inc, Seoul, 02841, Republic of Korea
• Youyoung Kim - Neuracle Genetics Inc, Seoul, 02841, Republic of Korea
• Minseok Kim - Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea
• Ji Yeon Lim - Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea
• Miri Kim - Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea
• Yebeen Kim - Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea
• Junwoo Lee - Neuracle Genetics Inc, Seoul, 02841, Republic of Korea
• Juwon Shim - Neuracle Genetics Inc, Seoul, 02841, Republic of Korea
• Jae Young Seong - Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea
• Joo Seok Han - Neuracle Genetics Inc, Seoul, 02841, Republic of Korea
• Sun Wook Hwang - Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea