Category: Scientific

https://www.zenbycat.org/blog/dr-pedersens-faqs-about-using-gs

Please note that these answers were provided by Dr. Pedersen individual cat owner. Consider them as a useful guide and not as individual veterinary advice. In no case do they replace standard veterinary care.

General questions about GS-441524 injection

What if my cat doesn't respond to GS immediately or her behavior doesn't change after a few weeks on the drug?

All we can do is watch what is happening over the next few days and hope for the best. If increased pain develops at the injection site, it is possible that this is the cause of the symptoms we are seeing. If the place is sensitive to touch, it goes without saying that it bothers the cat. It is possible that the situation will worsen and an open wound will form in the painful area, or it will improve quickly. Even if no one wants severe reactions at the injection site, injection is still a better choice.

My cat is experiencing “ups and downs” during treatment. Sometimes she seems full of energy, other times she is lethargic. Is this normal?

The most dramatic improvement usually occurs in the first week, or the first two, after which the process slows down. Do these cycles show that the cat is less active after the injection and more active a few hours after the injection? During our tests, we noticed that some cats seemed a little depressed and depressed after the injection. A higher dose worsens the situation. If it is a relapse, the reaction is even more pronounced, but if it is really just a reaction to the drugs, we will have to wait and see what happens after the end of treatment.

What should I do if my cat feels increased pain at the injection site from using GS? Would lidocaine or anything else help with the pain?

We are working to change the diluent for the drug to reduce stinging and pain, but it will probably take several more months and it will only solve the problem with the diluent and the effect of the drug itself. Applying lidocaine cream to the post-injection area is like locking the barn door after the horses get out. We tried to use it at the injection sites before treatment, but the owners who tried it were not satisfied with the results and stopped using it.

Is it safe / appropriate to continue administering FIO (feline interferon omega) concurrently with GS?

It won't help, it won't hurt either.

Should my cat continue in pre-zone with GS?

Not. You can stop prednisolone after a few days. A cat with FIP should respond very quickly to treatment and no other medication is needed at this time unless clearly indicated.

What are the chances that after a cat is cured of FIP, it will become infected again with a coronavirus that mutates again to FIPV? Should I treat a cat that secretes coronavirus?

Although theoretically possible, we have not yet seen the FIP-cured cats develop the disease later. Therefore, I would focus on curing your FIP positive cat. Do not treat a cat that only secretes enteric coronavirus. This cat has a very low risk of developing FIP and treatment with enteric coronavirus carriers will only promote the occurrence of drug-resistant strains.

Should I vaccinate or neuter my cat during GS?

Vaccination or castration is not required during treatment. Healing the cat is paramount. There will be plenty of time after treatment to resolve the issue of castration. Personally, I am not a strong supporter of FVRCP vaccines (polyvalent vaccines) or the need to vaccinate cats against rabies (unless required by state or local legislation) or administering FeLV to cats that are at low risk for infection. If we treat a cat with FIP, it should be treated in accordance with standard professional care, locality (rabies) and your practice. In short, treat the cat like any other cat, but have it cured first.

Questions about what will happen after the end of GS treatment

My cat has been with GS for several weeks and she seems to be doing well, but the titer of coronavirus antibodies is still high. Does that mean she's still sick? Should I be worried?

We do not see the coronavirus antibody titer value for you, so I cannot answer your question. However, we would expect it to take many months for permanent remission to occur. The fact that the titer is still high at this early stage does not worry us, but it may be something that should be monitored to catch a possible relapse.  But we are optimistic. Symptoms indicate complete remission, and just as importantly, the cat has gained weight and figure in recent weeks. These were also favorable symptoms in our other cases, which did not suffer from a neurological disease. The high titer of the coronavirus also reflects the intense response of the immune system to the FIP virus. It is desirable for this titer to remain high for a while and then slowly return to a much lower titer.

What if your cat relapses after you stop taking GS? How do I find out? (Question about a neurological cat)

We hope that your cat will remain healthy after the end of treatment, but we must also prepare for a possible relapse. Relapses can occur within 1-84 days, based on our experience with other cats we have treated. The clinical signs of relapse will be evident in neurological cases, and will be essentially a recurrence of the same problems. They get a fever, the cat stops eating, becomes less active and the neurological symptoms she had before return. It is important to document what is happening. You can also measure her temperature every day for several weeks and then every other day until we reach day 84. During this period, it will be important to monitor the cat's level of activity and weight.

What thermometer should I use to measure the temperature of a cat?

I prefer digital rectal thermometers, which are characterized by high measurement speed. Do you measure temperature during rest and not after a certain time of physical activity? Temperatures may vary. One is higher, one is higher.

I noticed that after the GS was discontinued, the cat's temperature rose sharply. Does that mean the cat has relapsed?

Cats and other small animals are not as consistent in their systemic temperature as humans, and the fluctuations you see are not uncommon. The problem is that the more you worry, the more you measure the temperature and the more of these fluctuations you will see. For this reason, we are not very afraid of these fluctuations. It is much worse when temperatures are consistently higher than 39.5 ° C. It is important to note the overall condition of the cat, its appetite, activity levels and clinical signs. In short, fluctuations like these are fine unless they become permanent and are associated with loss of appetite and activity. If your cat is otherwise well and there is no evidence of a persistent fever, we recommend that the cat be only at home, where it is possible to protect it from unnecessary stress and monitor it closely. 

Questions about laboratory results during or after GS treatment

My cat is being treated with GS and her lymphocyte count is high. That's all right?

The lymphocyte count is only slightly higher than normal, but in reality it is good. A low lymphocyte count would indicate that the infection is active and severe, while a high number would indicate that it elicits an immune response.

My cat has been on GS for several weeks and laboratory reports have increased creatine kinase and phosphorus. Is this a problem?

It doesn't have to mean anything if urea and creatinine are in the normal range. High phosphorus content may not mean anything yet. I recommend checking the values in a month.

We are concerned about the seemingly rapid increase in urea and creatinine in the blood. Do you have any other recommendations, or do you just need to supplement your fluids / diet and hope that the progression of kidney disease will slow down, as it is a young cat and it seems that the FIP has been successfully cured?

Yes, there is evidence of kidney damage and given the recent change and the fact that your cat is being treated this way, I think your cat may have suffered mild kidney damage. We only observed kidney damage that was milder than this in one of the more than 30 cats we treated for a total of 12-36 weeks and even at higher doses than you used. However, this type of medicine is known to be toxic to the kidneys in some people treated for HIV / AIDS or hepatitis C. This damage is reversible if you stop treatment early enough, and I assume you have already stopped treatment. If not, and you are at the end of 12 weeks or close, quit it. It does not reduce the chance of healing. Make sure the cat has access to water, and if her appetite is affected, feed her a moist diet that she likes with added water. Cats love wet food with juice and you can still mix a little extra water. There is a commercial and domestic diet for cats with kidney disease, but it is not very tasty and does not cure the kidneys, but rather protects the remaining kidney tissue. I would also make sure that your veterinarian does a urine test to find out what the specific gravity is - the lower it is, the greater the kidney damage. The more water cats drink and the more they urinate, the greater the kidney damage. It is necessary to determine whether the urine contains any signs of bacterial infection in the urine sediment or after cultivation - if they are found, antibiotics should be used immediately.

Questions regarding the oral form of GS

Some companies produce GS in tablet form. Is this form safe / effective?

Yes, at least one company in China also produces the oral form GS-441524, which it claims will work just like injections. This is not surprising, since the modifications required to convert injectable drugs into an oral form are well known. All drugs for HIV / AIDS and hepatitis C were also transformed into an oral form. However, like many others, you may find it more difficult to give tablets to cats than to inject. They usually adapt to the injections over a short period of time, but if they don't agree with the pills, it still gets worse and worse. Therefore, if you go this route, do not invest much in it until you are sure that you will be able to give the tablets to your cat.

Companies that make the oral form recommend splitting the dose and giving it twice a day. Why?

I do not know anything more about the oral form of GS, so I cannot provide a reliable answer to this question. However, there must be a reason why this Chinese manufacturer tells people to give GS twice a day and not once a day. Maybe it's because putting it all at once is too much of a burden for the cat system. It does not make sense to think that the medicine is excreted from the blood more quickly when given orally, which is another possible reason why they want to split the dose. It is important to me that these people are pushing hard for the oral form of the medicine, but have not provided any preliminary information on the success or tolerability, nor have any clinical trials been conducted.

 Is there a risk of alternating injection and oral forms of GS?

It would probably not be appropriate to alternate these forms on a daily basis. But there is probably no problem with the transition from one form to another. The diluted drug in injection form usually contains 15-16.5 mg / ml and the dose for cats is 4 mg / kg, SC.

Original article: https://sockfip.org/miscellaneous-advice-hormonal-neutering-and-vaccines/

The problems associated with adverse sexual behavior in intact cats and males during GS treatment have caught my attention. The questions often come from countries where castration is either postponed or not part of common practice. There are also frequent questions about routine vaccinations. There are concerns that stress during castration / sterilization or vaccination may affect the outcome of GS-441524 treatment. I am convinced that such fears are exaggerated. If a cat is treated and in remission, or is considered cured, it can be neutered, but preferably in the least stressful way. Cats can be neutered and returned to their homes quickly and efficiently on the day of neutering with a minimum of preoperative, surgical and postoperative treatments and restrictions (eg caging, e-collars). Such surgeries will be less stressful for cats (and owners whose behavior is reflected back on their cats) than intolerable sexual behavior alone.

I am not in favor of hormonal treatment to prevent inappropriate sexual behavior in cats, and I think that effective castration will be less stressful in the long run than such prevention. Therefore, if a permanent change in this behavior is required, surgical castration is always better than chemical castration.

Is it better to neuter cats if they still have some part of the treatment in front of them, provided they look healthy and blood test results are normal? Yes, castration during treatment makes sense. However, we do not recommend unreasonable resumption of treatment during surgical castration during the 12-week observation period after the end of treatment, the so-called post-treatment. Castration is unlikely to change the fate of a cat with FIP, as the cure for FIP is given by the very cessation of treatment. The observation period is not intended to further improve, but only to confirm the cure.

Some owners of cured cats do not want their castration for breeding purposes. We know that genetic and environmental factors also affect FIP, which has led to the recommendation that purebred cats that give birth to kittens with FIP should not be used for breeding. This should be even more true for cats that have been cured of the FIP.

When it comes to vaccines, many already know that I am not a big supporter of vaccines for cats after reaching adulthood, nor of boosted vaccines in the first year. I also think that rabies vaccines are not justified for normal use in cats, neither in terms of public health nor in cats. Nevertheless, I am aware that these views are not generally accepted and that laws in some states require rabies vaccinations against cats. In any case, we did not notice any consequences of vaccination in any of our cured cats. However, this is not something I would recommend for cats in treatment. The immune system of these cats is responsible for other things than responding to the vaccine.

When are drugs other than GS-441524 indicated for the treatment of FIP? - NC Pedersen

There are often questions about the need for complementary medicines to GS-441524. Initially, supportive (symptomatic) treatment may be needed to keep cats alive long enough for the antiviral effect to take effect. Drugs often used in this early stage usually include antibiotics (doxycycline / clindamycin), analgesics (opioids, gabapentin), anti-inflammatory drugs (corticosteroids, NSAIDS), immunostimulants (interferons, non-specific immunostimulants) and fluids. I have tried to avoid excessive use of these drugs, except for their temporary use, and only if there are legitimate reasons for their use, especially in severely ill cats during the first few days. The most important goal of FIP treatment is to stop the replication of the virus in macrophages, which immediately stops the production of numerous inflammatory and immunosuppressive cytokines that cause the symptoms of FIP. While some drugs, such as corticosteroids (prednisolone) or NSAIDS (meloxicam), can inhibit inflammatory cytokines, the only drugs that completely inhibit these harmful cytokines are antivirals, such as GS-441524 or GC376. These drugs lead to a dramatic improvement in fever, activity, appetite, etc. within 24-48 hours. This improvement will be much more pronounced than with any other medicine. Therefore, unless there are reasons to take other medicines, they should be discontinued as soon as there is a significant and stable improvement in FIP symptoms. I'm not even a supporter of the supplements that cats often take during treatment. B12 only treats B12 deficiency, not FIP anemia. This also applies to a wide range of nutritional supplements and many types of special cat food. Follow the proven commercial brands of cat food supplemented with animal meat.

Niels C. Pedersen, DVM PhD
University of California, Davis

Original article: INAPPROPRIATE USE OF GS-441524 IN AN ATTEMPT TO ELIMINATE FELINE ENTERIC CORONAVIRUS (FECV) FROM HEALTHY CATS

Mutian, the first Chinese company to sell GS-441524 on an unapproved market, recently advertised that using its oral formulation for one (or more?) Days would stop the fecal excretion of FeCV in healthy cats. Some veterinary researchers also take this approach. The reason is to prevent the formation of a mutant virus causing FIP (FIPV), and thus to prevent FIP. Although this approach is at first sight attractive, it is a very incorrect introduction of GS441524 in cats. Until now, GS441524 has only been recommended for the treatment of cats suffering from FIP. There are many problems associated with this approach.

In his advertisements, Mutian suggests that FeCV can be easily eliminated by a simple administration of oral GS441524. However, it does not talk about possible research that led to this approach. There is currently no published field research to demonstrate whether chronic FeCV excretion can be permanently cured by healthy cats. 40% or more individuals in any population of multiple cats may be positive for this virus. Naturally occurring FeCV infection appears at an early age and is not associated with any significant symptoms of the disease. Virus shedding takes weeks, months, and in some cases indefinitely, but in most cats it eventually stops building immunity. However, once immunity is stopped, antibody levels fall and cats become susceptible to infection again. This cycle of primary and secondary infections occurs in many cats throughout their lives. GS441524 treatment is very unlikely to result in more permanent immunity than is seen in nature. It would not be important if FeCV was short-lived in the environment and would not be easy to transfer to clothing, rubbish, hair and other items. FeCV survives in the environment for up to 2 weeks and transmission by contaminated objects is well documented. Therefore, although it is possible to treat FeCV in a particular cat, the virus easily returns to the population. This has also been documented in the experience of isolating mothers and prematurely weaning their kittens, which is a slightly similar strategy to preventing FeCV infection.

Although our current knowledge of FeCV infection calls this approach into question, there may be more compelling reasons not to treat healthy cats with GS441525 or any other safe and effective antiviral drugs in the future. It is unlikely that the excretion of FeCV can be stopped for a significant period by a single or short-term treatment, as stated, and this will undoubtedly require a longer period. This approach will be extremely expensive if applied to a large number of cats in a kennel, shelter or rescue station.

The most important reason to avoid this FIP prevention approach is the problem of drug resistance. We already know that some cats with naturally occurring FIP are infected with one or more GS441524-resistant FIPV strains. Our field experiment with 31 cats found that one was infected with a virus that was highly resistant. There is laboratory research confirming that resistance can develop very easily in cell cultures. Drug resistance is also well known in viral diseases such as HIV / AIDS and in people infected with the hepatitis C virus. The fastest way to achieve resistance to any microbes, including viruses, is to overuse drugs where they are not needed. The problem of antimicrobial drug resistance is sufficiently confirmed by our experience with bacteria in animals and viruses in humans. There is no doubt that overuse of drugs such as GS441524 in large groups of healthy cats will lead to a positive selection of FeCV strains that are partially or completely drug resistant. This resistance is also manifested in the mutant FIP-causing FeCV virus (FIPV), which precludes the use of GS441524 in a larger number of cats with FIP. Unfortunately, veterinary medicine does not have the resources of human medicine or financial incentives to discover, test and obtain multiple drug licenses in order to circumvent the acquired drug resistance.

I urge cat owners and scientists to refuse to use safe and effective antivirals in this way. I have nothing to do with voracious drug manufacturers who prefer profit to serious science, common sense and the fears of cat owners suffering from FIP now or in the future. There is a saying, "Just because we can do something doesn't mean we should." NC Pedersen

Original article: Dr. Pedersen on Relapses and Post-GS Treatment; 14.8.2019

Is it possible that GS-441524 will lose its effectiveness, leading to relapses?

In particular, GS-441524 is extremely stable in the highly acidic solution used by its suppliers. We stored it in the fridge for months. The more likely reasons for relapses are inadequate treatment (poor injection, poor medicine), inability to get enough medicine in places with inflammation (such as the brain), or drug resistance (we saw this in 1 cat in both our GC376 and GS studies). -441524).

Are secondary infections such as toxoplasma or infectious anemia associated with relapse?

This is very unlikely for secondary infections that lead to relapse. Cats are the ultimate host for Toxoplasma gondii and the infection is rarely systemic. In fact, the systemic form is so unusual compared to FIP that there is no good clinical reason for its routine testing in cats suspected of having FIP. In addition, toxoplasmosis would be much more likely to occur in outdoor cats that hunt than in shelter or indoor cats that are fed commercial feed. Infectious feline anemia, which is caused by a common and largely overt blood infection with one or more types of hemotropic mycoplasma or hemoplasm, could break into clinical form upon immunosuppression by another infectious agent. However, I cannot recall the case of FIP, which was complicated by these organisms. However, feline leukemia virus, and not coronavirus, is strongly associated with hemotropic mycoplasma. Nevertheless, I suspect that this is one of the reasons why so many veterinarians include doxycycline in the cocktail of drugs they used to "treat" the FIP.

Should cats receive Virbagen omega after GS treatment to strengthen the immune system?

Published double-blind, placebo-controlled studies of feline interferon omega in FIP have shown that it has no therapeutic benefit. I also perceive this with other immunomodulators such as PI.

Should I try to eliminate feline enteric coronavirus (FECV) from my cat's environment after the cat is no longer treated with GS-441524?

This virus is so ubiquitous, difficult to eliminate, and easily reinfected that I have come to the conclusion that attempting to eliminate it will be very costly and largely unproductive. Although it is possible to eliminate FECV in a small group of cats that are kept in strict isolation and by faecal testing, in reality it is easier said than done. In the end, even if you succeed with great effort and cost, what will you do then ?! The only way to maintain the situation is to observe an extremely strict quarantine of cats and people moving in and out of your premises, which greatly complicates the ability to maintain a functional shelter or rescue or kennel.

How useful is the AGP test to find out if my cat is cured?

The AGP test is popular in Europe, but I can't figure out why. The test measures what we call the "phase reactant" and is a measure of inflammation in the body. It is completely non-specific and has no added value compared to routine examinations, such as general health, weight loss, fever, abnormalities in white blood cell parameters, albumin and globulin levels, A: G ratio, etc.

Original article: Ending FIP, Is There Hope? A Summary of Dr. Niels Pedersen's Presentation at the Winn Feline Foundation Symposium (29.6.2017)

Summary: Carol Johnson DVM, PhD. A Heather Lorimer Ph.D.
For clarification, additional information from literature articles by Dr. Pedersena.

Feline Infectios Peritonitis (FIP) is one of the most complex infectious diseases and is undoubtedly one of the worst diseases imaginable. It is caused by an RNA virus from the coronavirus family Nidovirales. Other RNA viruses that the reader may be familiar with include the Ebola virus, influenza virus, AIDS, and rhinoviruses. Coronaviruses are named after protrusions that look like a crown (or corona) when viewed under an electron microscope. Coronaviruses can cause disease in almost every animal species, but as such, coronaviruses are species-specific: feline coronaviruses do not infect humans, dogs, or other animals.

Feline enteric coronavirus (FECV, also referred to in the literature as FCoV) usually remains in the intestinal tract and infects the upper layer of cells lining the small intestine before settling in the large intestine. FECV can cause mild diarrhea and vomiting, but is not considered a serious pathogen in the intestinal tract.

An FECV-infected cat can shed the virus in large quantities and excretion can continue for months. Cats are obligatory carnivores and, as a result, have a very short digestive tract. This may play a role in high virus shedding. Immunity to FECV is usually temporary and previously immune animals may be reinfected. This is one of the reasons why vaccination prevention is difficult, if not impossible.

FECV specific mutations they allow him to leave the intestinal tract, where he infects cells of the immune system called macrophages, which usually help fight infection. This mutated version of FECV is called FIPV (feline infectious peritonitis virus). Infected macrophages spread the disease in the cat's body in a similar way as tuberculosis (TB) bacteria spread in humans or animals. FIPV-associated mutations occur in three parts of the FECV genome, but a particular mutation may be unique to each cat. As many as 20% FECV infections can lead to subclinical macrophage infection, but relatively few cats develop FIP. Similarly, up to 40% of the world's human population is infected with tuberculosis bacteria, but few people have developed complete tuberculosis. Unlike TB, FIPV is not transmitted to other cats; the transmission takes place via an unmutated FECV.

FIP is a population-related disease high-density cats, where kittens are part of the equation. Kittens are most susceptible to developing FIP and are usually infected with FECV at about 9 weeks of age. In general, FIP can also occur in a dense urban or rural population of free-range cats. In the United States, FIP is more common in cats and kittens from conventional, high-density shelters and feline shelters or rescue stations where kittens may be exposed to large viral loads. Another source of FIP are kennels. Not only are a number of cats concentrated in farms, but there may also be genetic predispositions that may also play a role (up to 50% in some cases). Although the genetic risk is clear, genetic analysis shows that susceptibility to FIP is likely to involve a large number of genes. As a result, inbreeding is associated with susceptibility to FIP, but genetic testing for this susceptibility is not currently possible. Overall, FIP occurs in about 0.3% cats, but can occur in up to 1-5% (or more) cats in high-density sites, such as kennels or rescue stations.

The FIP is on the rise probably due to the increasing number of rescued cats in which kittens can be fed from bottles, weaned prematurely and exposed to large amounts of FECV.

There is a dry and wet form of FIP, but there may be combined forms and it is possible to change from one form to another. In general, the moist form, characterized by effusion, which leads to enlargement of the abdomen or fluid in the lungs, along with other symptoms, has a rapid course and can kill the cat very quickly (in this case, it is often death due to euthanasia). The dry form can last for months to about a year, sometimes longer.

Risk factors for FIP development they include the prevalence of cats that shed FECV, the intensity of virus shedding, the number of cats aged 4 to 29 months (most sensitive) and genetic predisposition (in bred cats). FIP often occurs in young cats after a stressful event, such as castration or sterilization. In these cases, the cat may already have FIPV-infected macrophages in the lymph nodes, and stress allows FIP to break out.

FIP can also develop in older cats. It typically happens that one (or more) cats in a multi-cat household die due to old age and the owner feels that the remaining cat needs a new friend, so he gets the kitten out of the shelter. The older cat has long since lost immunity to FECV and is now susceptible to infection. Due to older age, an older cat may have a worse immune response than a younger animal and is more likely to develop FIP.

Dr. Pedersen is of the opinion that FIP can usually be diagnosed relatively easily. Kittens or young cats with a viscous, slimy, yellow-colored fluid in the abdomen or thoracic cavity are likely to have FIP. The dry form of FIP may be more difficult to diagnose, but in young cats it is usually a combination of symptoms associated with chronic ill health, including weight loss, cyclic fever, characteristic blood count (anemia, decreased albumin, increased globulin, low albumin to globulin ratio, increase in absolute neutrophil count, decrease in absolute lymphocyte count, increase in bilirubin, etc.) and coronavirus titre ≥ 1: 3200, which helps to guide the diagnosis of FIP. Dry FIP may present with neurological symptoms such as convulsions or ocular lesions. Autopsy of most cases confirms characteristic lesions and leads to characteristic histological findings. Tissue or histological specimens can be further tested by various techniques, such as polymerase chain reaction (PCR), immunofluorescence (IFA) (frozen tissue only) or immunohistochemistry (IHC) (formalin-fixed tissue), but Dr. Pedersen considers these tests to be confirmatory. He believes that in almost all cases it is possible to diagnose FIP by routine examination. Some diagnostic tools lead to false negative results. For example, PCR, a commonly used diagnostic test, has about 30% false negative results.

Traditional treatment does not work. Immunosuppressants such as corticosteroids may make the cat feel better, but the course of the disease will not change. Biological agents do not work. Vaccines do not work because the kitten is usually infected with FECV before vaccination and because the immunity is only temporary. The most common cause of death in cats with FIP is euthanasia due to loss of quality of life as the disease progresses relentlessly. Although the wet form of FIP is often very fast, some cats may live longer with supportive care than one might think (weeks or months). Pulmonary fluid should be aspirated, but abdominal fluid should generally not be aspirated. Dry cats can stay alive for months or more. Spontaneous remissions may occur, but usually all cats eventually succumb to FIP.

Hope comes in the form of new antivirals. RNA viruses share many of the same types of genes and therefore present similar goals in drug development. This means that drugs designed to block one type of RNA virus may prove useful in the treatment of another type. Two potential drugs that may be effective in the treatment of FIP are protease inhibitors and nucleoside analogs (NUCs), which specifically target viral enzymes. RNA viruses often form one very large protein, which is cleaved by very specific proteases into the individual viral proteins needed to assemble new viruses. Drugs that inhibit specific proteases have been developed as antiviral drugs for various viruses. NUCs used to prevent HIV genome replication (reverse transcriptase inhibitors) in AIDS patients may also block RNA-dependent RNA polymerases that replicate the coronavirus genome. Cats, like all mammals, do not have an RNA-dependent RNA polymerase, so it is an enzyme specific for a given virus. Protease inhibitors act in the late phase of cell infection, while NUCs act in the early phase.

GC376, a protease inhibitor, was the first drug of its kind to be studied in cats. Dr. Pedersen worked with a team of veterinarians and chemists at Kansas and Wichita State Universities to treat cats experimentally infected with FIP, and later naturally infected cats. The treatment included 20 naturally infected symptomatic cats with FIP. Thirteen eventually died, some relapsing after remission and death due to neurological FIP. Seven cats survived and now appear to be free of disease, one to 1 year after treatment. A study in symptomatic, naturally infected cats determined a safe dose of drugs and determined an optimal treatment time of 12 weeks. However, treatment of cats with neurological symptoms was not successful, probably because the drug does not cross the blood-brain barrier. The drugs had few adverse effects; one of the most pronounced was the inhibition of adult tooth formation, which is a known side effect of this group of drugs. The limiting factor in the study was the final amount of drug produced.

EVO984 is a nucleoside analogue - reverse transcriptase inhibitor developed by Gilead Sciences. NUCs may have some advantage over protease inhibitors because they act in the early stages of virus infection of the cell. Gilead has provided several NUCs for which Dr. Pedersen tested their effectiveness against FIPV in vitro, followed by a pharmacokinetic study and finally a study in cats with artificially induced FIP. UC Davis needed to obtain extensive documentation and knowledge before treatment could be done on client pets with naturally developed FIP, and this study is underway right now. The drug appears to be safe, has been able to reverse the symptoms of FIP, including effusion, and some cats have successfully entered remission. Like GC376, EVO984 is not effective on neurological FIP because it does not cross the blood-brain barrier well. Although this study has only been running for a few months, it looks more promising than GC376. The test has only lasted 12 weeks, but all 24 cats that took part are currently alive.

Translator's note: EVO984 later became known under a new name, which is known to almost everyone who treated a cat with FIP. EVO984 is nothing but GS441524. In addition, GS441524 has been shown to cross the blood-brain barrier at increased doses and thus to treat neurological forms of FIP.

Next steps: While the studies appear promising, many unanswered questions remain. Dr. Pedersen believes that if his study is successful, it will likely need to be confirmed by a second group. It has been pointed out that additional funding may be needed through the Winn Feline Foundation’s Bria Fund, which has invited contributions for future FIP research. Gilead is excited about the preliminary results, but the company develops drugs for human use and does not have an animal health division. Gilead has indicated to Dr. Pedersen that if the results continue to be promising, they may pursue it or seek a partner that specializes in animal health products. However, given the overall prevalence of FIP worldwide, the drug may not be attractive enough for large pharmaceutical companies. However, Dr. Pedersen pointed out that there may be a way to find a way around it using provisions of the FDA’s Minor Use and Minor Species Animal Health Act of 2004.

Questions and Answers:

The question was asked why more cats could not be treated in the study. The drugs are experimental and have limited supplies. Dr. Pedersen feels that he only needs about 20 cats to draw conclusions, as this is usually a deadly disease. He also said that the desperate owners sometimes offered him a large amount of money so that their cat could be included in the study. He said it was very sad, but strict criteria had to be followed to be included in the study and it was not possible to meet everyone.

Asked about the genetic predisposition and whether it is possible to select purebred cats resistant to FIP, Dr. Pedersen shared his experience with randomly selected breeding cats experimentally infected with the highly lethal FIPV laboratory strain. Despite infection, about 20% cats did not develop FIP. When these cats were housed together, their kittens did not develop FIP in only about 10%. When the second generation of surviving cats were bred together, FIP developed in all their offspring. Dr. Pedersen believes that these results support the concept that the most resistant cats are crossbred cats, where many immune system genes are heterozygous (having two different versions of each gene), so that a cat's immune system can respond and attack a wider range of pathogenic targets. He believes that when cats are bred, the cat's immune system becomes more homozygous (they have two copies of the same version of each gene), which reduces the variety of targets to which the immune system can respond. Because mutations that change FECV to FIPV vary, cats with a broader ability to respond to small viral changes are likely to be better protected. Breeders should minimize the use of males that have fathered kittens that have died of FIP. Why males? Because individual breeding males generally produce more offspring than breeding females, they therefore have a greater impact on the next generation of cats.