Fifty years’ fascination with FIP culminates in a promising new antiviral

3/25/2019, Translation 5/1/2021
Niels C. Pedersen
Original article: Fifty years' fascination with FIP culminates in a promising new antiviral

Feline infectious peritonitis (FIP) has fascinated me for the last 50 years. Although FIP is caused by a virus, it most closely resembles mycobacterial infections, which cause tuberculosis and leprosy in humans and cats. The disease revealed its secrets very reluctantly, and each new discovery led to further questions. As Robert Frost's famous poem puts it: "We dance around the ring and assume, but the secret sits in the middle and knows." I'm lucky to have reached the last milestone of my career when I identified safe and effective FIP treatment. We were able to reach this vase only thanks to hard work and great cooperation with teams of people in the USA from places like Kansas State and Wichita State University or Gilead Sciences.

We know that small molecules targeting specific proteins involved in RNA virus replication are able to safely treat various forms of FIP. These small molecules include the protease inhibitor GC376 and the nucleoside analog GS-441524. Both are based on drugs that are currently used to treat common human diseases, such as hepatitis C and HIV / AIDS, and are tested for exotic infections called MERS (Middle East Respiratory Syndrome), SARS (Severe Acute Respiratory Syndrome). and Ebola.

It is important to note that the small clinical trials we have completed and published are intended primarily to validate the concept, but unfortunately not to be quickly translated into approved and commercially available products. Some investigational drugs may be preferred (and thus delayed for veterinary use) in human medicine, and all will require a lengthy process to obtain final approval, even for animals. Private veterinary pharmaceutical companies will ultimately be responsible for their marketing. Is the demand for such medicines and the willingness of owners to bear the costs a sufficient incentive for these companies?

The FIP relinquished its secrets with great reluctance, and each new discovery led to further questions.

Figure 1. Bubba was originally found as an abandoned 3-week-old kitten by its owner in Florida, USA. He was diagnosed with dry abdominal FIP at the age of 7 and enrolled in treatment study GS-441524.
(a) In May 2017, just before the start of treatment, Bubba weighed 6 kg (13.5 lb). In the first week of the 12-week treatment, his owner stated that he "ate alone, alert, energetic and playful."
(b) Bubba, shown in January 2018, weighing 9.3 kg (20.5 lb).
Acknowledgments: Adel Gastle

Unfortunately, initial reports of successful treatment only stimulated the desperate owners' efforts for immediate access to these drugs and created a growing black market. Therefore, I suspect that we will test our patience and ethics over the next few years. None of this should detract from the fact that, after more than 50 years of research, we have reached this important point. Much more is waiting to be discovered. How does virus replication in macrophages lead to immunity in many cats, while in unfortunate individuals it leads to disease? Can this knowledge finally lead to effective vaccines? What is the best way to care for kittens in kennels, shelters and deposits to minimize FIP losses? Are even better drugs awaiting their discovery? Can small molecule inhibitors act in synergy with each other in a completely different treatment modality?

I will leave these and other questions to my scientific colleagues in the field of FIP.

Niels C Pedersen DVM, PhD
Center for Pet Health,
School of Veterinary Medicine,
University of California, Davis, USA

References

  • Pedersen, NC, Perron, M, Bannasch, M. Efficacy and safety of the nucleoside analog GS-441524 for the treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg 2019; 21: 271–281.
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