Cannabinoid receptors as new targets for HTLV-1 associated myelopathy (HAM/TSP) treatment

Afsane Fadaee; Fatemeh Sadat Mohammadi; Nazila Ariaee; Sanaz Ahmadi Ghezeldasht; Narges Valizadeh; Fatemeh Kheradmand; Reza Boostani; Houshang Rafatpanah; Seyed Abdolrahim Rezaee

doi:10.1016/j.msard.2024.105659

Cannabinoid receptors as new targets for HTLV-1 associated myelopathy (HAM/TSP) treatment

Mult Scler Relat Disord. 2024 Apr 29:87:105659. doi: 10.1016/j.msard.2024.105659. Online ahead of print.

Authors

Afsane Fadaee¹, Fatemeh Sadat Mohammadi², Nazila Ariaee², Sanaz Ahmadi Ghezeldasht³, Narges Valizadeh², Fatemeh Kheradmand⁴, Reza Boostani⁵, Houshang Rafatpanah¹, Seyed Abdolrahim Rezaee⁶

Affiliations

¹ Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran; HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Ahmad Abad Bolv., Mashhad, Iran.
² Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran.
³ Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR), Razavi Khorasan, Mashhad, Iran.
⁴ Immunology Research Center, Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁵ HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Ahmad Abad Bolv., Mashhad, Iran.
⁶ Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran; HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Ahmad Abad Bolv., Mashhad, Iran. Electronic address: RezaeeR@mums.ac.ir.

PMID: 38704874
DOI: 10.1016/j.msard.2024.105659

Abstract

Background/aim: The roles of endocannabinoids are described in immune modulation and neuroprotection. HTLV-1-associated myelopathy (HAM/TSP) is an inflammatory neurodegenerative disease. Therefore, in this study, the interactions of HTLV-1 regulatory factors and host cannabinoid receptors (CBRs) were evaluated in HAM/TSP.

Methods: Nineteen HAM/TSPs, 22 asymptomatic carriers (ACs), and 18 healthy controls (HCs) were enrolled. RNA was extracted from PBMCs and then reverse-transcribed to cDNA. The gene expression of CB1R and CB2R, as well as HTLV-1 proviral load (PVL), Tax and HTLV-1 basic leucine zipper factor (HBZ) were assessed by RT-qPCR.

Results: The mean expression of CB1R in ACs (8.51 ± 2.76) was significantly higher than HAMTSPs (1.593 ± 0.74, p = 0.05) and also HCs (0.10 ± 0.039, p = 0.001). The CB2R gene expression level in ACs (2.62±0.44) was significantly higher than HAM/TSPs (0.59 ± 0.15, p = 0.001) and HCs (1.00 ± 0.2, p = 0.006). Meanwhile there was a strong correlation between CB1R and CB2R gene expression levels in the HCs and HAM/TSPs (p = 0.001). HTLV-1-Tax expression in HAM/TSPs (386 ± 104) was higher than ACs (75 ± 32) and statistically significant (p = 0.003). While HTLV-1-HBZ was only expressed in three AC subjects and five HAM/TSPs, thus it cannot be analyzed.

Conclusion: The up-regulation of CB2R has immunomodulatory effects in inflammatory reactions. While CB1R as a neuroprotective agent may suppress inflammatory reactions in ACs, preventing HAM/TSP. It seems that, like multiple sclerosis (MS), cannabinoid medications are beneficial in HAM/TSP.

Keywords: CB1 receptor; CB2 receptor; Cannabinoids; HTLV‐1‐associated myelopathy/tropical spastic paraparesis; Human T-lymphotropic virus 1.