Thursday, March 14, 2013

Laminitis Research: Grayson-Jockey Club Foundation Announces 2013 Support for New and Continuing Laminitis, Lameness Detection Projects

Today the board of directors of Grayson-Jockey Club Research Foundation announced funding of 12 new research projects in addition to five projects that are now in their second year. The 17 research projects are being unwritten by the foundation in 2013 for a total of $874,024.

Three of the projects have relevance to laminitis research and are profiled in this blog post. In addition, one project has relevance to lameness detection.

A full list of all funded projects is available on the Foundation's web site.

The project summaries were provided by the researchers and/or the Foundation.

Dr. Hannah Galantino–Homer, University of Pennsylvania
First Year (2 Year Grant)

Dr. Galantino–Homer
The goal of this study is to improve the understanding and early diagnosis of equine laminitis. Equine laminitis is a disease that affects the suspension of the bone of the foot, and hence the weight of the horse, to the hoof capsule via the interdigitating lamellae of the hoof and underlying connective tissue. Laminitis causes failure of digital suspension resulting in excruciating pain and often resulting in humane destruction of the horse. 

Our previous studies, using archived samples from two experimental models of laminitis, detected molecular changes that are helping us understand the steps preceding full-blown laminitis. In human diseases, molecular changes in the affected tissue are often reflected in molecular changes in the blood. These “disease markers” can then be used to diagnose early stages of a disease, when therapies are the most effective.

Our preliminary studies have determined that one of our potential markers is elevated in blood samples from an experimental model of laminitis and from horses with laminitis associated with a non-weight-bearing orthopedic injury (supporting limb laminitis). The goal of the proposed study is to identify at least three serum markers that would be useful for diagnosing the early, inapparent or “developmental” phase of laminitis and to detect the resulting tissue damage and the body’s immune response to that damage.

Based on our earlier studies, we will investigate blood levels of specific proteins using samples from horses without laminitis, horses in the early stage of the disease prior to lameness, and horses with overt laminitis. The studies will involve methods for the identification and quantification of proteins in tissue and blood samples and for the detection of specific classes of antibodies involved in the immune response.

Positive results from this study will then be used to develop diagnostic tests to detect incipient laminitis in horses that are believed to be at risk of developing the disease, such as horses with a prior history of laminitis, severe orthopedic injuries, colic, obesity, or horses that have ingested excess grain, and to assess lamellar tissue damage. New technology that allows the “multiplexing” of assays for several markers into a single assay will be used to generate an assay for lamellar tissue damage.

Dr. James Belknap, The Ohio State University
Second Year

Dr. Belknap

A recent USDA study indicates that approximately 1% of all horses in the USA suffer from laminitis at any given time, and approximately 5% of those animals die or are euthanized while many others remain crippled. Of the conditions which create laminitis, the development of the disease in the supporting limb of an already injured horse is one of the worst, since it is believed that 50% of those cases result in euthanasia.

The author reports that while there are hundreds of published papers in the literature about other forms of laminitis, reports on supporting-limb laminitis are restricted to clinical reports and case studies. This project will "introduce a novel, non-painful model of supporting-limb laminitis and will allow for cutting edge bench research techniques to not only (1) test the current hypotheses on the cause of laminar failure, but also (2) provide an unbiased technique to determine the cellular events that occur . . ."

The investigator has performed a number of laminitis project for Grayson and the USDA, and has a well developed set of tools and techniques including laser microdissection of frozen laminar cells and an advanced "functional genomic" technique called RNA-Seq. By applying these techniques that have previously characterized laminitis caused by sepsis or metabolic syndrome to support limb laminitis, we will get our first understanding of what kind of drugs and treaments might prevent it. This grant was selected by the board to receive the sixth annual Elastikon™ Equine Research Award.

Dr. Alan Nixon, Cornell University
Second Year

Dr. Nixon
The initial fervor associated with stem cell therapies has been tempered by mediocre clinical results," states Dr. Nixon, long recognized as a key leader in quest to maximize use of stem cells. "More can be done, including pre-differentiation, gene-directed lineage targeting, and more efficient delivery."

This proposal will deliver by "local vein injection, to back-flow to bowed tendon and other disease conditions such as founder and traumatic arthritis." Transplanted cells then exert normalizing and restorative effects . . ."

The long-range goal is to provide a simplified approach to stem cell therapy. We cannot do this without verification of cell homing and impact. (The project) will map stem cell distribution in the tendons, ligaments, and joints of the forelimb after direct venous injection."

Dr. Kevin Keegan, University of Missouri
One Year

Dr. Keegan
This project addresses development of an objective method (i.e., using measurements performed by a calibrated instrument) for detection of obscure, subtle lameness in horses at the gallop with a relatively low cost and that can be used in the field will contribute for significant advancements in the understanding of the causes and mechanisms of lameness in the race horse.

This new method will also be useful for studying the relevance of the findings of clinical examination as well as the effectiveness of current and new treatments, and of preventive prophylactic measures.

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