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FIP Studies Move Forward with Hope


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Feline Infectious Peritonitis (FIP) has remained a mystery for years. Recent work, funded by the Winn Feline Foundation Bria Fund and the Morris Animal Foundation has   is unraveling that mystery

FIP is a disease of cats, which usually affects kittens. According to SOCK FIP,  1 in 100 to 1 in 300 of all cats under ages three to five will die as a result of FIP. The incidence can be five to 10 times greater among young cats coming from catteries and shelters. FIP is considered 100 percent fatal, and there is no treatment or cure. FIP can manifest suddenly — weeks, months or even years after initial infection. Therefore, cat lovers usually experience the heartbreak of this disease long after they have developed strong emotional bonds with their pets. Because most often FIP touches kittens – little babies – it’s even more heartbreaking.

Commonly cats (and many mammal species) suffer from the enteric corona virus. In fact, the symptoms are typically so mild that cat caretakers don’t notice. No matter, nearly always the corona virus (in people one of the “common colds”) resolves itself in kittens. But in some kittens, the corona virus inside the cat mutates into an immune mediated disease which is FIP.

From the Winn Feline Foundation Bria Fund:

Tanaka Y, Sato Y, Sasaki T.  Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B.  J Gen Virol. 2016 Nov 21.

Cat expert Steve Dale offers FIP updatesThere is an important and unique immunological component to the pathology of the disease and there is evidence that some immunosuppressive drugs may offer hope for a treatment.

In this report, researchers from Nippon Veterinary and Life Science University, Tokyo, Japan investigated the mechanism by which the cyclophilin (Cyp) inhibitor, cyclosporine A (CsA), inhibits replication of some corona viruses, such as FIP. Cyclophilins are peptidyl-prolyl isomerases (PPIase), which are important for various physiological functions, but also appear to be necessary for replication of some corona viruses.  When CsA binds to cyclophilin, the complex inhibits calcineurin, a calcium-dependent enzyme that is important in T-cell activation.

By knocking out expression of two cyclophilin isoforms, CypA and CypB, the researchers showed that both cyclophilin isoforms are required for efficient viral replication in FIP-infected cells.  In addition, expression of mutant CypA and CypB with predicted mutations in the PPIase active sites decreased viral replication in FIP-infected cells.  Mutations at PPIase active sites drastically reduced the affinities between CsA and CypA, further supporting the importance of the PPIase active sites for viral replication.

These findings suggest that PPIase active sites of Cyps are required for FCoV replication.  Potential therapeutic effects of PPIase inhibitors, such as CsA, in combination with other therapeutic agents should be further evaluated and determine the possible role of CsA, or other PPIase inhibitors, as part of a FIP treatment cocktail. Cat expert Steve Dale offers FIP updates

Merran Govendir-Veterinary Pharmacology Unit at SydneySchool of Veterinary Science, University of Sydney, Australia is studying to determine if a medication mefloquine may potentially be a treatment for FIP. Mefloquine is a medicine that has been administered to people to prevent malaria. It has been in the news over the past year as it was given to the Australian Defence Forces personnel to prevent malaria and has reportedly resulted on some adverse side effects.

So before mefloquine is given to sick cats with FIP, the aim of their project is to obtain as much information as possible on how the feline body is likely to deal with mefloquine. In people, mefloquine is metabolized by the liver. The cat is known to have trouble metabolizing some medicines, so this project is to investigate if the cat will take longer to metabolize the mefloquine than people or dogs.  If the cat is taking longer to metabolize the mefloquine than other species, then researchers there need to know this and reduce the dosage accordingly if clinical trials go ahead.

Meanwhile, Morris Animal Foundation funding products (often in conjunction with the Winn Feline Foundation)  is advancing understanding in how this virus affects some cats and not others, as well as identified new targets for novel treatments.

Cat expert Steve Dale offers FIP updatesRecent advances in molecular biology are helping us understand how FIP virus causes disease through mutations in the coronavirus.  Morris Animal Foundation wants to capitalize on these discoveries, and has made FIP an even bigger priority with newly funded studies:

  •  two genetic studies that focus on how viral mutations help the virus invade critical cells of the immune system
  •  development of a novel vaccine strategy against feline enteric coronavirus, the nonlethal virus that can mutate into the FIP virus
  •  a clinical trial to investigate if a novel antiviral drug can cure or greatly extend the lifespan and quality of life for cats infected with the FIP virus
  •  investigation of two genetic mutations that may be a reliable indicator of FIP in cats, and provide the basis for development of an accurate diagnostic test.

Animal shelters dread FIP. Despite it’s name FIP itself is NOT contagious. However, the corona virus which causes FIP is VERY contagious. And its thought the sometimes crowded shelter conditions, and the stress related to being there allows FIP to occur often in shelters (and catteries).

“This is a tough situation with no easy answer,” said Dr. Kate Hurley of the UC Davis Koret Shelter Medicine Program. “We know the other kittens are at higher risk, but there’s no test to tell which, if any, will go on to get ill.”

What we do know, said Hurley, is that “because disease can develop any time within about 18 months after exposure, and maintaining these kittens in the stressful situation of a shelter will only increase risk; quarantine is not an option. Additionally, if they happen to be infected with, and shedding, a particularly virulent strain of coronavirus — one more likely to mutate to FIP in an individual cat — keeping them in the shelter is not an optimal plan for the other kittens in the facility.”

Hurley suggested the best option, if it’s possible, is to sterilize the kittens and then house them in informed foster care without other kittens while looking for homes for the littermates.

For more information on FIP in animal shelters, visit the UC Davis Koret Shelter Medicine Program website’s FIP information center.

 

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