Research proposes that existing treatments could treat chikungunya

Transmission electron micrograph of Chikungunya virus particles Credit: Wikimedia commons

According to a recent research by scientists from A*STAR, it was suggested that the existing auto immune therapies used for other conditions could be used to treat the Chikungunya virus (CHIKV) infection.

Insights into how symptoms of the chikungunya virus are triggered, suggests existing treatments could be repurposed to help infected patients.

CHIKV causes high fever, headaches, joint inflammation and debilitating joint pain when it is transmitted to humans, by mosquitoes. Since 2004 there have been major outbreaks in Africa, Asia, the Caribbean, and South and Central America. There are currently no approved treatments.

A group led by Lisa Ng at the A*STAR Singapore Immunology Network (SIgN) demonstrated in 2013 that CD4+ T cells, which mediate immune system responses, play a central role in triggering CHIKV-induced joint swelling.

To investigate, Ng and Laurent Renia, her colleague at SIgN led the team to transfer CD4+ T cells from both healthy and CHIKV-infected mice into T cell receptor-deficient mice. Only those that received cells from infected donors suffered joint swelling, inflammation and skeletal muscle damage — confirming the key role of these T cells in triggering CHIKV symptoms.

They then carried out proteome wide screening assays in which CD4+ T cells taken from CHIKV-infected mice were tested against all proteins generated by the CHIKV virus.

This identified specific segments in two viral proteins, nsP1 and E2, as those that stimulate CD4+ T cell responses to CHIKV. The discovery could be used to help design vaccines against CHIKV and related viruses.

Applying their findings, the researchers treated groups of CHIKV-infected mice with three clinically-approved T cell suppressive drugs – Fingolimod, Cyclosporin A and Rapamycin. Tissue samples were then visually assessed by histopathologists.

The degree of subcutaneous edema during Chikungunya infection (top) and the fingolimod treated mice (bottom) during the peak of joint swelling. From © Teo et al., some rights reserved; exclusive licensee American Association for the Advancement of Science.

Fingolomid, usually used to prevent multiple sclerosis relapses, successfully reduced joint swelling, inflammation and muscle damage in the rodents. It did so both when given as a prophylactic, and following infection as a standard therapeutic treatment. The other two drugs — cyclosporin A and rapamycin — failed to control the disease symptoms in mice.

Ng and her colleagues stress that the use of fingolomid to treat CHIKV patients with chronic joint pain has yet to be evaluated, but hope their study will lead to further research on whether it and other immunosuppressive drugs could help those with the condition.

“We were pleased with these findings,“ says Ng. “They demonstrate our previous theory about the pathogenic role of CD4+ T cells was correct, and suggest existing T cell suppressive drugs could provide viable treatment options for patients.” 

The group believes such drugs could also be used to treat inflammation caused by other arthropod-spread viruses that are mediated by virus-specific CD4+ T cells.

This article is reproduced from A*STAR Research