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A gift funds innovative Lyme research

Medicine@Yale, 2019 - November December

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Instead of targeting the Lyme bacterium, the goal is to block the mechanism of infection

The Steven & Alexandra Cohen Foundation has pledged $1.8 million over three years to fund Lyme and tickborne disease research by Erol Fikrig, MD, Waldemar Von Zedtwitz Professor of Medicine (Infectious Diseases) and professor of epidemiology (microbial diseases) and of microbial pathogenesis. The gift will fund Fikrig’s novel approach to developing an anti-tick vaccine. Instead of trying to target the Lyme disease-causing bacterium, Borrelia burgdorferi, as other approaches have, Fikrig plans to target the Ixodes tick that spreads disease, essentially by stymieing the tick’s ability to take a blood meal.

“The Steven & Alexandra Cohen Foundation has provided good resources, so we can go at it full steam ahead,” says Fikrig, an expert in diseases spread by insects and ticks who also is chief of the Infectious Diseases Section of the Department of Internal Medicine and a Howard Hughes Medical Institute investigator.

“Let’s say you’re drinking a drink out of a straw, and the straw gets clogged,” Fikrig explains. “That’s what we’re trying to work on—blocking [the tick] from feeding.”

When ticks first bite, they inject proteins that prepare a favorable environment for a meal—the event during which various pathogens can be transmitted to the host. These proteins block blood clotting, inflammation, and immune responses. Fikrig’s vaccine would prevent them from functioning, encouraging the tick to give up, drop off, and look for another mammal to bite.

Unlike with a mosquito, which can inject pathogens immediately after biting, it takes a tick up to 48 hours after biting before introducing Borrelia into the host. That delay gives researchers their opening. In studies of guinea pigs, Fikrig’s lab has already found that the animals can resist tick bites based on immunity to proteins that the tick produces in the first 24 hours of attachment. Such immunity not only prevents the tick from feeding, but also impairs infection with Borrelia.

That discovery lines up with another line of evidence from people living in areas endemic to Lyme disease: Those who have been bitten often by ticks that don’t carry Borrelia seem to acquire some protection from the parasites over time. “Many will tell you ticks don’t bite them as well as they used to,” Fikrig says. These people’s bodies may be creating antibodies to the ticks’ salivary proteins.

Fikrig’s lab is currently examining thousands of tick-saliva proteins to find the most promising targets. Once they have cloned 15 to 20, the team will begin testing them in animal models.

“This is an innovative approach to stopping Lyme infection, which remains very difficult both to diagnose accurately and to treat effectively,” says Alexandra Cohen, who launched the Cohen Lyme & Tickborne Disease Initiative in 2015. “Lyme is one of the fastest-growing diseases in the United States and is terribly debilitating for far too many people who are infected.”

Approximately 300,000 people contract Lyme disease in the U.S. each year, and the numbers are thought to be increasing. Most live in the Northeast and upper Midwest, a distribution likely to expand with climate change. The disease can cause short-term flulike symptoms and rash; over the long term, it can cause facial paralysis; arthritis; inflammation of the heart, brain, or spinal cord; and fatigue, among other problems. Symptoms can persist long after antibiotic treatment. A previous human Lyme vaccine called LYMERix that targeted Borrelia burgdorferi sold poorly and was withdrawn from the market in 2002.

Since its inception in 2001, the Stamford, Connecticut-based Steven & Alexandra Cohen Foundation has funded projects in multiple areas, including Lyme and tickborne disease, underserved communities, children’s health and education, the arts, and sustainability. Inspired by Alexandra Cohen’s personal struggle with Lyme disease, the foundation has committed over $60 million to more than two dozen projects addressing prevention, diagnosis, treatment, education, and ecology.

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