Improving treatment of chronic pain in cats

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Winn grant W12-027
Development of outcome assessment instruments for chronic pain in cats
Investigator: Dorothy Cimino Brown; University of Pennsylvania

Cats are unique. They cannot benefit from the same pain fighting medications used in dogs, because they can cause serious side-effects in cats. It is crucially important that we identify pain fighting medications that are safe and effective in cats, so that we can relieve them from pain caused by such conditions as arthritis or cancer. Once a treatment option for pain is identified that might be useful in cats, studies must be carefully designed in order to prove that the potential new treatment option is effective. The greatest obstacle to designing such studies is the fact that we have not developed reliable ways to measure pain in cats. If we can not measure the pain, we can not prove that we are appropriately treating it. 

The goal of this study is to develop tools that can measure pain in cats and therefore appropriately design studies that will identify new treatments. The first tool is the Feline Brief Pain Inventory, which will be an owner completed questionnaire that will allow them to identify and report on how their cat behaves at home, focusing on the behaviors that are related to pain. The second tool is an activity monitor that can be worn on the cat’s collar while it progresses through its normal activities at home. We plan to identify how many days the monitor needs to be worn to collect data reliably. Ultimately the monitor might identify the improved activity that can be related to adequate pain control.

This project is available for sponsorship. When you sponsor a project, your name will be added to the list of the project's supporters on our website and in any publications we produce about the project. You will receive exclusive pre-publication reports on the progress of your chosen project as they become available, and a final report at its conclusion.

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New feline virus identified

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Lau SK, Woo PC, Yip CC, et al. Identification of a novel feline picornavirus from the domestic cat. J Virol. 2012; 86: 395-405.

Picornaviruses are small viruses infecting many animal species as well as humans. This family of viruses includes many important human and veterinary pathogens including the common cold virus, poliovirus, and foot and mouth disease virus. Thus far, picornaviruses infecting cats have not been identified. 

The investigators screened fecal, urine, blood, and nasopharyngeal swab samples from over 600 cats in Hong Kong over a 3-year period for picornavirus using genetic detection methods. They found a novel virus which after characterization was found to be most closely related to but distinct from all known picornaviruses. Their findings indicated that infection of cats with this virus was quite common. While the cats tested in this study were all apparently healthy, further research is required to fully understand the significance of this virus among cats. [MK]

Related articles: Santti J, Vainionpaa R, Hyypia T. Molecular detection and typing of human picornaviruses. Virus Res. 1999; 62: 177-83.

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Inherited blindness in Bengal cats

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Winn grant W12-022
Molecular characterization of Bengal progressive retinal atrophy
Investigator: Robert A. Grahn; University of California, Davis
 
Inherited blindness is a devastating disease common to many species. In people, over 25 different forms of inherited retinal blindness have been clinically characterized. Cats also have several forms of blindness that destroy the photoreceptors at the back of the eye. These conditions will randomly occur in a particular cat breed and then will be inherited. Some forms of blindness attack the photoreceptors shortly after birth, while other forms take longer to destroy vision. Several Bengal cats have been diagnosed with a form of blindness that destroys their vision at around 5 months of age. A genome wide association case control study has indicated a candidate region for a possible mutation causing progressive retinal atrophy in the Bengal breed. This proposal will obtain the sequence of the RNA and DNA of this candidate gene to identify the mutation and allow for development of a genetic test to help reduce the prevalence of the disease in the Bengal breed.
This study has received partial funding from Winn according to our guidelines for breed-specific projects. Please donate so that the project may be fully funded.

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Hypertrophic cardiomyopathy in the Sphynx cat

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Silverman SJ, Stern JA, Meurs KM. Hypertrophic cardiomyopathy in the Sphynx cat: A retrospective evaluation of clinical presentation and heritable etiology. J Feline Med Surg 2012;14:246-249.

Hypertrophic cardiomyopathy (HCM) is the most common form of heart disease in the cat. HCM is a heritable disease in some breeds of cats such as the Maine Coon and Ragdoll. Distinct causative mutations have been found in these breeds and there may be other clinical presentations. This suggests that HCM In cats is a diverse disease. The Sphynx breed has been reported to have a predilection for HCM. The records of 18 cats (11 female, 7 male) were evaluated for characteristics of HCM and for a familial etiology. The age range of affected cats was 0.5 to 7 years (median, 2 years). The results indicate a familial disease, at least in some cases, with multiple (four) affected cats occurring within one family. The mode of inheritance suggests an autosomal dominant trait similar to that of the Maine Coon, though a prospective breeding project would be needed to determine the exact mode. The age of onset appears to be younger in Sphynx than other cat breeds studied. Further studies are warranted to evaluate for a causative mutation. [VT]

Winn has recently funded grant W12-009: Fine mapping for Sphynx cat hypertrophic cardiomyopathy gene.

Related articles: Meurs KM, Norgard MM, Kuan M, et al. Analysis of 8 sarcomeric candidate genes for feline hypertrophic cardiomyopathy mutations in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2009;23:840-843. 

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Let's immune system help

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Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido, 
Vinod P Balachandran, et al. Nature Medicine17 (2011) 


I would like to hilight this paper to our readership, as many of your are involved in the design of clinical trials and selection of potential biomarkers. This report is one of a handful of high impact papers that report the coperative role that inflammatory infiltrate and non cell autonomous effectors play in modulating response to established agents. This study demonstrates an interesting immunological mechanism of Imatininb  that contributes to the antitumor effect in a Gastrointestinal Stromal Tumor (GIST) mouse model. Inflammatory infiltrate is a known finding in GIST specimens (including intratumoral CD8+ Tcells, Treg cells and macrophages). Acording to the authors, Imatinib activates CD8+ T cells and induces Treg cells apoptosis within the tumor. Imatinib is therefore able to reduce the expression of 2,3-dioxygenase (Ido) of tumor cells. Ido enzyme is involved in the catayzation of immunosuppressive metabolites from tryptophan and therefore mediates downstream immunological response. Interestingly Imatininb resistant tumors, generally as a result of a second KIT mutation, restore the overexpression of IDO and combination of Imatinib with CTLA-4 blockade (a well established immunotherapeutic strategy) act synergistically. This insight provides some hints on something we have been suspecting for a long time. It is easy to predict consequences for rational design of combination therapies and strategies to overcome resistance in Imatinib resistant tumors.TweetShare

Treatment of blood clots in cats with heart disease

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Each year, the Winn Feline Foundation receives proposals from veterinary researchers around the world who are interested in improving feline health. To date, Winn’s cumulative total in feline health research funding exceeds $4 million. Forty-four proposals were submitted by researchers seeking funding in this review cycle. This year, our team of veterinary consultants helped Winn select 10 projects for funding, for a total of $174,018. Here is one of those projects:

W12-037
The efficacy of bosentan, a mixed ETa ETb receptor antagonist, in cats with arterial thromboembolismInvestigators: Elizabeth Rozanski, Gareth Buckley; Tufts University
A Ricky Fund Project
Hypertrophic cardiomyopathy is a very common heart disease in cats. One of the most devastating complications of heart disease is development of blood clots called feline aortic thromboembolism (ATE), which cuts off the blood supply to one or more limbs. ATE is associated with a survival rate of less than 40% despite multiple efforts to try to improve outcomes. It is important to cats and their owners to be able to offer an intervention that improves survival with a good quality of life. Cats are recognized to have “reactive” blood vessels, and this response may worsen the outcome in ATE. The arteries in cats suffering from ATE will release various chemicals including one called endothelin. Endothelin causes an increased tendency to form more clots, and promotes severe inflammation and narrowing of collateral vessels supplying areas behind the site of the clot. Bosentan is a drug used successfully in people to treat various diseases such as coronary artery disease. This study looks to determine the effectiveness of bosentan in the treatment of cats with ATE.
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Improving treatment of cancer in cats

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Each year, the Winn Feline Foundation receives proposals from veterinary researchers around the world who are interested in improving feline health. To date, Winn’s cumulative total in feline health research funding exceeds $4 million. Forty-four proposals were submitted by researchers seeking funding in this review cycle. This year, our team of veterinary consultants helped Winn select 10 projects for funding, for a total of $174,018. Here is one of those projects:

W12-005
Immunohistochemical quantification of the transcobalamin II protein (TCII) and receptor (TCII-R) in naturally occurring feline tumors
Investigators: Annette M. Sysel, Joseph A. Bauer; Bauer Research Foundation, Akron OH

Cancer affects millions of cats annually and may account for 1/3 of all disease-related feline deaths. There are only 2 FDA-approved drugs available for the treatment of cancer in animals, but both drugs are licensed exclusively for use in dogs. Treatment of cancer in cats is largely extrapolated from treatments used in human and canine medicine. A new and interesting approach to cancer therapy is based on the fact that cancer cells rely on vitamin B12 (cobalamin) to grow and they produce transport proteins to scavenge cobalamin. An anti-tumor drug called nitrosylcobalamin (NO-Cbl) uses cobalamin to target cancer cells via the transcobalamin II (TCII) transport protein and receptors. The TCII protein and receptors have been evaluated in human and canine tumors, but not yet in cats. In this project, the investigators will quantify the TCII protein and receptor in feline tumors with the goal of identifying tumors that may be susceptible to treatment with drugs such as No-Cbl.

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