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

Mult Scler Relat Disord

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:

Published: July 2024

AI Article Synopsis

  • * Researchers compared gene expression of cannabinoid receptors CB1R and CB2R among 19 HAM/TSP patients, 22 asymptomatic carriers, and 18 healthy controls, finding significant differences in expression levels.
  • * The results suggest that increased CB2R levels may help modulate immune responses, while CB1R may protect the nervous system in asymptomatic carriers, indicating potential benefits of cannabinoid treatments for patients with HAM/TSP, similar to benefits seen in multiple sclerosis.

Article 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.

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Source
http://dx.doi.org/10.1016/j.msard.2024.105659DOI Listing

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