2006 Miller Trust Grant Awards
February 6, 2007 (published)
Winn Feline Health Foundation

EveryCat Health Foundation
(formerly Winn Feline Health Foundation)

George and Phyllis Miller Trust
San Francisco Foundation
Six studies funded for a total of $87,515

Expansion of the Shelter Population Index for Cats: Phase 2 of a Multi-institutional Study.
John C. New, Jr., DVM, MPH, DACVPM, University of Tennessee. $21,330

A multi-institutional coalition has developed a Shelter Population Index (SPI) that estimates the number of cats entering and leaving selected shelters including their sources and dispositions. Similar to the Dow Jones Industrial Average that measures the general health of an important economic domain, the SPI is designed to measure the performance of the overall sheltering system. In addition, the SPI is reflective of the general awareness and involvement of the community that supports the feline sheltering system rather than an evaluative instrument for individual shelters. The dynamics of feline shelter populations will be linked to communities using Combined Statistical Areas as defined by the U.S. Census Bureau. The SPI can be used to justify and track improvement of community-based measures aimed at controlling the surplus of cats in the U.S. By repeated collection of reliable data, the SPI will enable the identification of trends associated with shelter cat populations and community-based solutions. Through increased awareness and tracking, communities will become more responsive to the factors that result in the surplus of cats that must be dealt with by shelters. The specific goals of this study are to develop a consistent and standardized reporting method for animal shelters, provide reliable data for community decision makers, strengthen the science base for shelter animal medicine, improve the animal sheltering system by linking to community-based characteristics, and increase public awareness of the magnitude of the problem of homeless, abandoned, marginalized and feral cats in the community.

Gabapentin for analgesia and anesthesia in cats.
Bruno H Pypendop, DrMedVet, DrVetSci, DACVA, University of California at Davis. $8,400

Pain management in cats has traditionally relied on opioid or non-steroidal anti-inflammatory drug (NSAID) administration. However, both classes of drugs have undesirable characteristics. Gabapentin is a gamma-amino-butyric-acid (GABA) analogue. Gabapentin has been shown to be efficacious in the treatment of chronic pain syndromes. More recent evidence suggests that gabapentin may also decrease pain and opioid consumption after surgery. Although use of gabapentin in cats has been anecdotally reported, to our knowledge, no data on the effect of this drug in cats are available.

Gabapentin has characteristics that make it a potentially good option to provide analgesia in cats. It is widely available as an oral preparation. Studies in various species have shown very little toxicity associated with the administration of gabapentin.

Moreover, while many drugs require glucuronide conjugation for their elimination, a pathway in which cats are deficient, gabapentin appears to be excreted unchanged by the kidney.

The effects of gabapentin are thought to be related to a selective inhibitory effect on voltage-gated calcium channels. Because other drugs with analgesic and anesthetic activity, such as halogenated anesthetics, also act on voltage-gated calcium channels, it is possible that gabapentin would potentiate their effects. To our knowledge, this hypothesis has not been tested in any species. I

n this study, we propose to determine the pharmacokinetics of gabapentin in cats, to examine the effects of gabapentin on the minimum alveolar concentration of isoflurane, to examine the effects of gabapentin on thermal and mechanical pain, and to establish the dose-dependence of these effects.

Genetic Testing for Feline Blood Groups.
Leslie A. Lyons, PhD, University of California, Davis. $15,000

The domestic cat has only one identified major blood group. The common types have been shown to be allelic, type A dominant to type B, however, the very rare type AB is not well defined. Cats have naturally occurring alloantibodies to the blood types, thus, transfusion reactions can be immediate, particularly during the first transfusion of a type B cat with type A blood. These alloantibodies lead to neonatal isoerythrolysis for type A and type AB kittens born from a type B queen. The antigens that determine blood type in cats are defined and are principally due to the form of the neuraminic acid residues presents on a ceramide dihexose backbone on the surface of the erythrocytes. Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) converts the different acid residues. The objective of this proposal is to identify the causative mutations for the feline blood types in the CMAH gene. Six DNA variants are 100% concordant with serologically determined blood types of cats from different breeds and these mutations cause amino acid changes in the protein. Additional cats from all available breeds will be genotyped for the identified mutations in order to clarify the truly causative mutation. Cats from unrelated populations, remote populations and different breeds will help to distinguish which mutations cause the blood types. The serologically based assays can not distinguish Type A homozygote cats versus cats that are heterozygote Type A, carrying the recessive B allele. A DNA-based assay will be cheaper, can be performed earlier, and will detect carriers.

Tissue factor: Initiator of thrombosis and potential therapeutic target in cats with cardiac disease?
Tracy Stokol, BVSc, PhD, DACVP, Cornell University. $19,751

Cats with cardiac dysfunction frequently develop thromboembolic disease. In particular, aortic thromboembolism (ATE) causes severe pain and high mortality, with up to one third of cases succumbing to this devastating syndrome1,2. Survivors are typically treated with anti-platelet drugs (clopidogrel, aspirin) or anticoagulants (heparin, warfarin), in the hopes of ameliorating the thrombotic tendency1-5. Empiric therapy, however, has not proven to reduce the recurrence of ATE. New drugs are urgently needed to target the events that initiate thrombosis.

Tissue factor (TF) is the physiologic stimulus for coagulation6,7. TF-bearing cells (e.g. fibroblasts, smooth muscle cells) at sites of endothelial injury support coagulation cascade activation and local generation of high concentrations of thrombin. In pathologic states, TF expression is upregulated on circulating monocytes. This aberrant TF expression promotes systemic thrombin generation and intravascular thrombosis.

Our preliminary data indicate that thrombin mediates the hypercoagulability of feline cardiac disease. We hypothesize that induced TF expression on circulating monocytes stimulates thrombin generation, thereby promoting the thromboembolic events associated with cardiac syndromes. If this hypothesis proves correct, then inhibition of TF represents a novel approach for treating ATE. Tissue factor pathway inhibitor (TFPI) is the primary inhibitor of TF and recombinant human TFPI shows promise in anticoagulant treatment trials8,9. In order to define the role of TF in feline hypercoagulability, we aim to: 1) Measure TF activity of feline monocytes; and 2) Test the ex vivo TF-inhibitory activity of recombinant feline TFPI. Our long-term goal is to develop feline recombinant TFPI for thromboprophylaxis of feline ATE.

Comparison of Two Drug Protocols for Clearance of Cytauxzoon felis Infections.
Leah A. Cohn, DVM, PhD, DACVIM, University of Missouri. $8,284

The protozoal pathogen C. felis causes a disease of extreme morbidity and mortality in domestic cats. Until now, it was believed that the cat was a "dead end" host for the organism, and that domestic cats only become infected after being bitten by a tick that had previously fed on an infected Bobcat. Bobcats undergo a limited mononuclear-schizongenous stage of infection (the stage responsible for clinical disease) but then maintain the red blood cell -piroplasm stage of infection indefinitely. It is the piroplasms that transmit the parasite to ticks when they feed. Recently, there have been published and anecdotal reports of domestic cats that survive the schizont-induced disease state. It appears that domestic cats which survive infection remain parasitemic for years. Recovered cats might be able to serve as a reservoir host for tick infection, and thereby propagate infection in the domestic cat population even in urban and suburban areas where Bobcats do not thrive. If this is true, treatment that allows survival of domestic cats without eliminating the organism may increase the opportunity for infection of other cats that might otherwise not become infected. Therefore, it is important that the ability of anti-protozoal drugs to clear the infection entirely be investigated. We have identified a unique population of healthy but infected cats. We propose to compare two anti-protozoal drug regimens, imidocarb dipropionate versus atovaquone and azithromycin, for their ability to eliminate the protozoal organism C. felis. We hypothesize that atovaquone and azithromycin will cure infection more often than imidocarb dipropionate.

Screening for Antibodies to the 7b Protein of Feline Coronavirus in Cats for Detection of Persistent Infection.
Melissa Kennedy, DVM, PhD, University of Tennessee. $14,750

Feline coronavirus (FCoV) is the etiologic agent of feline infectious peritonitis (FIP), a fatal systemic disease of cats. It is most common in multi-cat households and catteries. The factors leading to disease production remain unknown, as not all FCoV-infected cats develop the fatal disease. Virus mutations have been theorized to lead to production of a virulent phenotype. These mutations may arise during virus replication in an infected cat. Previous investigations have shown that some animals remain infected and shed virus for extended periods. These animals may be a source of mutated virus. Control of FIP in cattery situations is designed to eliminate these chronically infected cats. Identification of these animals relies on repeated genetic detection assays on feces collected over time to document chronic infection and shedding which is not only time-consuming, but expensive.

A simple test done at a single time point would be optimal. Our previous investigation has shown that expression of the 7b protein occurs in many FCoV infections (9). We found high levels in cats with FIP but also in cats without FIP. Some of the latter animals were housemates of FIP victims, and two cheetahs 7b-antibody positive were known to be persistently infected. We speculate that the 7b protein may play a role in persistent infections; thus animals with significant antibody levels to the 7b protein may be chronic shedders of the virus. We propose to investigate this hypothesis by testing client-owned cats for antibody to the 7b protein and fecal FCoV shedding. Initially, screening of animals will be done to identify those shedding FCoV. These animals will then be tested over the next year for fecal shedding of FCoV by Real Time PCR and for 7b antibody levels. Correlation of virus infection with shedding and 7b antibody levels will be evaluated. This investigation may lead to development of a rapid, simple, and inexpensive test for persistent FCoV infection.