Wednesday, June 8, 2016

Combination therapy cures Babesiosis in mice

Mon Jun 6, 2016 4:11 pm (PDT) . Posted by: 

"Rick Laferriere" ri_lymeinfo 

*Combination therapy cures tick-borne illness in mice*
Press Release
By Ziba Kashef, /Yale News/, Yale University, New Haven, Connecticut

June 6, 2016

A novel combination therapy cures an emerging infectious disease, 
babesiosis, which is transmitted by the same ticks that transmit the 
agents of Lyme disease, said Yale researchers. This "radical" therapy 
not only clears the infection but also prevents the recurrence that 
often occurs with existing treatments.

The study was published online June 6 in The Journal of Experimental 
Medicine <>.

Babesiosis (bab-e-see-oh-sis) is caused by the /B. microti/ parasite, 
which is most often transmitted through tick bites. It is more common in 
the Northeast and northern Midwestern states, and likely is on the rise 
as infected ticks expand geographically. Infected individuals can be 
asymptomatic, or develop symptoms that range from mild and flu-like to 
severe and life threatening. The parasite can develop resistance to 
existing therapies, leading to relapses after treatment.

For their study, the Yale-led team first tested in mice with diminished 
immune systems four drugs that are currently used in the form of two 
combinations to treat human babesiosis. Only one of those drugs, 
atovaquone, was effective in attacking a target enzyme that, when 
mutated, allows the parasite to develop resistance. Using the mouse 
model, the team observed efficacy with a fifth drug (ELQ) that involves 
a similar mechanism of action as atovaquone but at a different enzyme 
target site. They decided to test the two drugs in combination.

The researchers found that the combination of atovaquone and ELQ-334, at 
low doses, cleared the infection and prevented recurrence up to 122 days 
after treatment.

"This is the first radical cure against this parasite," said Choukri Ben 
Mamoun, associate professor of infectious diseases. "The novelty of the 
study was identifying a combination therapy that will both kill the 
parasite and also paralyze the target enzyme, making it nearly 
impossible for the parasite to develop resistance."

The finding is significant since babesiosis is increasing and up to 19% 
of the ticks and up to 42% of the mammalian hosts (mice and other 
rodents) that carry the bacteria that cause Lyme disease is co-infected 
with /B. microti/.

With this finding, Ben Mamoun and his co-authors can take the next step 
and pursue studies of the combination therapy in people. "We are 
developing a better analog for ELQ that will be used in clinical trials. 
That's what our future studies will focus on — identifying a better ELQ 
that could be added to atovaquone. We could test the safety of the 
compound in humans," he said.

Other study authors include Lauren A. Lawres, Aprajita Garg, Vidya 
Kumar, Igor Bruzual, Isaac P. Forquer, Isaline Renard, Azan Z. Virji, 
Pierre Boulard, Eduardo X. Rodriguez, Alexander J. Allen, Sovitj Pou, 
Keith W. Wegmann, Rolf W. Winter, Aaron Nilsen, Jialing Mao, Douglas A. 
Preston, Alexia A. Belperron, Linda K. Bockenstedt, David J. Hinrichs, 
Michael K. Riscoe, and J. Stone Doggett.

The research was supported by the National Institutes of Health and the 
U.S. Department of Veterans Affairs Biomedical Laboratory Research and 


Yale News <>
Yale University
Office of Public Affairs & Communications
2 Whitney Avenue, Suite 330
New Haven, Connecticut 06510


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