Repurposed Drug Straightens Out Chikugunya

Researchers from Singapore have shown that an existing immune suppressing drug can be used to treat debilitating joint pain caused by the mosquito-borne virus.

AsianScientist (Feb. 7, 2017) – A drug originally approved for treating multiple sclerosis has now been found to reduce joint inflammation caused by chikungunya virus (CHIKV) infection in mice. The report, published in Science Translational Medicine, lays the groundwork for future clinical studies to determine if the drug—known as fingolimod—can also be used to treat CHIKV-induced joint pathology in humans.

CHIKV, a mosquito-borne virus, currently infects more than six million people worldwide. Infected individuals often experience debilitating muscle and joint pain, which can persist for months to years after infection. Indeed, “chikungunya” derives from a Makonde word meaning “to walk bent over,” reflecting the stooped posture adopted by afflicted patients.

Despite evidence that CHIKV-induced joint inflammation is mediated by immune cells, the precise mechanisms behind it remain poorly understood. In addition, because no drugs that specifically treat the disease are as yet available, patients are typically given generic non-steroidal anti-inflammatory drugs that have limited efficacy.

“Most research groups focus on developing antivirals or small molecules that target the virus. However, in CHIKV infection, there is only a short window for antivirals to have maximum effect. Importantly, in most patients, severe joint inflammation persists after the virus has been cleared,” said Dr. Lisa Ng of the Singapore Immunology Network at the Agency for Science, Technology and Research, who led the study.

“We wanted to identify the cause of joint inflammation induced by the virus, and explore treatment regimens using clinically approved immune-based drugs.”

To study this, the researchers used a mouse model that closely mimics the joint characteristics seen in human CHIKV infection. Mice that lacked T cells, they found, did not develop joint inflammation upon virus infection. But when the researchers transferred a subset of immune cells—CD4+ T cells—that specifically recognized the virus into these mice, the animals developed severe joint inflammation during CHIKV infection.

Since these data suggested that virus-specific T cells were responsible for the inflammation, the researchers went on to test several clinically approved T cell-suppressive drugs for their ability treat it. Of these, only fingolimod was successful; the researchers found that it works by retaining T cells in the lymph nodes, thus preventing them from migrating into the joints.

“The identification of CD4+ T cells as the main mediator of acute chikungunya joint swelling provides a basis for other research groups to identify targeted approaches to treat this disease,” Ng told Asian Scientist Magazine. “Since fingolimod is already clinically approved, safety trials in humans will not be needed to use this drug for treatment of joint inflammation in chikungunya patients.”

One limitation of the study, said Ng, is that the mouse model is only reflective of acute disease in humans; further studies are needed to assess the drug’s ability to treat chronic joint pain.

The researchers are now looking to test fingolimod in chikungunya patients, as well as to determine if the drug is effective against inflammatory disease caused by related viruses.


The article can be found at: Teo et al. (2017) Fingolimod Treatment Abrogates Chikungunya Virus–Induced Arthralgia.

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Copyright: Asian Scientist Magazine; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Shuzhen received a PhD degree from the Johns Hopkins Bloomberg School of Public Health, USA, where she studied the immune response of mosquito vectors to dengue virus.

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