Gene therapy for laminitis?

Thanks to a research breakthrough at the Uni-versity of Pennsylvania’s New Bolton Center, it may one day be possible to treat laminitis using gene therapy that targets damaged cells within the hoof.

An often debilitating inflammation of the hoof’s sensitive laminae, laminitis is notoriously difficult to treat. “The issue with laminitis is that the damaged tissue [the lamellae] is highly specialized,” explains Dean Richardson, DVM. “The tricky thing is effectively treating this highly specialized tissue when we really are not entirely sure of what ‘targets’ within that tissue need to be treated.”

Richardson and his research team have been investigating the potential for gene therapy techniques to fundamentally alter cells within the hoof. “Gene therapy in this sense means that you define a gene that codes for a protein that you believe will be therapeutic. That gene is then inserted into a virus,” he explains. “Viruses are built to do one thing—get their genetic material into a host cell. Once that genetic material is in the host cell, it makes the proteins coded for by the virus. In natural viral infections, this means that the host cells manufacture many copies of the virus itself. In gene therapy, the viral vectors are ‘crippled,’ meaning they are incapable of replicating themselves, but they still have the machinery to enter the host cell.”

Once a viral vector containing the desired gene enters a host cell, it makes the host cell produce the desired protein, says Richardson. “That protein is expressed locally and (theoretically) treats the disease process.”

The researchers tested this technique on seven healthy horses with no history of laminitis, using “marked” genes that could easily be identified after delivery by one of six different viral vectors. The vectors were injected into the hoof through the palmar digital artery, which runs down the side of the pastern. A technique called regional limb perfusion was then used to ensure that the virus—and the gene it delivered—stayed within the foot for 30 minutes.

Seven to 21 days later, the researchers found that three of the viral vectors had penetrated cells throughout the hooves, including the laminae. These vectors were even more widely dispersed when combined with a surfactant, a substance that reduces surface tension of a liquid and increases its spreading and wetting properties.

Learning that viral vectors can deliver genes to hoof tissue is only a preliminary step in the complex process of creating a gene therapy, says Richardson. Next the researchers will work to determine which genes can be beneficial. “This is the ultimate question,” he says. “Right now we have used some candidate genes [specifically , tissue inhibitor of metalloproteinase-3 (TIMP3)] but we don’t know which or even how many candidates there may be because no one has completely defined the pathogenetic pathways of laminitis.”

This article was originally published the March 2016 issue, Volume #474 of EQUUS magazine




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