Research into gene therapy for osteoarthritis

Osteoarthritis, or degenerative joint disease, causes pain and suffering to horses and humans alike.
University of Florida researchers are developing a gene therapy for osteoarthritis in horses, in the hope that the technique will be applicable to people as well. The goal is to create a one-time treatment that gives long-term benefits.
The work involves the use of viruses, called adeno-associated viruses, or AAV, to deliver genetic material to the joints of horses, where it would produce a therapeutic protein directly at the site of the disease.
There is no cure for osteoarthritis. Current medications often only produce limited relief, require repeated administration and may interfere with healing. In contrast, this new gene therapy would require a one-time treatment and would not hinder the body’s healing processes.
Research suggests that the pain, joint inflammation and loss of cartilage associated with osteoarthritis are linked to a protein called interleukin-1. A therapeutic gene used to treat the arthritic joints produces a second protein that naturally counteracts the effects of interleukin-1, but that has not yet translated into effective treatments for patients because of difficulty getting high enough concentrations inside affected joints.
The UF researchers are devising a gene therapy approach that would allow continued production of therapeutic protein within the joints, directly at the disease site.
“We hope that this will be at least the first step in a therapy that will benefit both people and animals,” said Patrick Colahan, a board-certified equine surgeon in the University of Florida College of Veterinary Medicine and co-investigator on the study. “It has the potential to help lots of different species, and from a veterinarian’s perspective, that’s what we’d like.”
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Foal heat diarrhoea - no treatment best

New research shows that the bacterial population of the foal's digestive tract undergoes major changes within the first two weeks of life. This change seems to be directly responsible for the "foal heat" diarrhoea that is often seen in young foals.

The work, carried out at the University of Veterinary Medicine, Vienna and the Graf Lehndorff Institute for Equine Science, Neustadt, Germany, found that the onset of diarrhoea was unrelated to the mare returning to oestrus after giving birth.
 
Horse-breeders expect most newborn foals to suffer from diarrhoea. Many methods have been suggested to avoid the problem, including supplementing the mothers’ diets with ß-carotene, which is known to be helpful in preventing diarrhoea in young calves.  However, Juliane Kuhl in the group of Christine Aurich at the University of Veterinary Medicine, Vienna has now shown that this food supplement has no real effect on the incidence of diarrhoea in foals.

Kuhl, Aurich and their collaborators examined the bacteria in the faeces of foals and their mothers, as well as the measuring the levels of antibodies (γ-globulins) in the animals’ blood. 

They found little change over time in the nature of bacteria in the mothers’ faeces, although they did observe dramatic differences in the bacteria in the foals’ faeces. 

Foals are born with very low amounts of bacteria in their intestines but are colonized by E. coli within the first day of their lives.  In contrast, the number of foals with Enterococcus remains low until about ten days following birth, after which these bacteria can be detected in most animals.  Other bacteria such as Streptococcus and Staphylococcus arrive between two and four weeks after birth, by which time the foals’ intestinal flora is essentially indistinguishable from that of their mothers.

Interestingly, the researchers found that the changes in the bacterial flora closely parallel the development of diarrhoea. 

They also found that foals with low γ-globulin levels did not develop diarrhoea more often than those with much higher levels. So, the incidence of diarrhoea cannot be related to a weakened immune system.

Kuhl is careful to note that “we have not yet shown that diarrhoea results directly from the switch in intestinal bacteria, although our data make it seem very likely that this is the case.”

The implication is that the horse is essentially predisposed to develop diarrhoea at a very young age.  As the condition clears up fairly quickly without the need for antibiotic treatment, food withdrawal or food supplements such as ß-carotene, breeders should simply accept that many of their animals will suffer from the condition. 

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Comparing hot iron branding and microchipping in foals

Research shows that foals find both hot iron branding and microchip implantation stressful, but the effects of microchip implantation do not last as long.

The study, by R Erber and colleagues, compared the response of groups of foals to the two methods of identification..

Fourteen warmblood foals from the Brandenburg State Stud were divided into two groups. Seven foals were branded with a hot iron on the right thigh; the others had a microchip implanted in the neck.

Throughout the procedure the researchers monitored the foals for signs of stress by recording heart rate, and concentration of cortisol in saliva. They also monitored how the foals behaved in response to the procedures.

Both procedures caused stress. Foals showed an increase in heart rate and in saliva cortisol concentration. In fact, foals showed two peaks in heart rate - initially when they were first restrained, and again when the actual identification (branding or microchipping) procedure was carried out.

Although there was no difference in the degree of stress (measured by salivary cortisol and heart rate) between the two procedures, the researchers point out that it was possible that the foals' response to restraint could have masked that due to the procedure itself.

However, the researchers did find a difference between the two procedures. Hot iron branding resulted in skin necrosis that got worse for three days after application. It also produced an increase in skin temperate.

In fact, not only did foals show an increase in skin temperature at the site of the hot iron branding, they had increased skin temperatures on the opposite thigh and on both sides of the neck as well.

So although both procedures appeared to cause similar degrees of stress, hot iron branding produced more persistent changes. It resulted in skin necrosis that lasted for at least seven days. Hot iron branding also resulted in a generalised increase in body temperature that was not seen after microchip implantation.

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Seasonal pasture myopathy research

University of Minnesota researchers are seeking the help of horse owners to find out more about Seasonal Pasture Myopathy. This condition, which is frequently fatal, has been identified increasingly in the Midwestern US.

Horses with Seasonal Pasture Myopathy (SPM) suffer from severe, generalised muscle weakness. They are often unable to get to their feet, or only do so with difficulty. If they are still able to walk, they have a stiff gait - especially of the hindquarters. Affected animals have elevated heart rates, and show profuse sweating and muscle twitching. They often have increased respiratory rates. Dark brown colouration of the urine is characteristic. The mortality rate can exceed 90%.

“We have already seen suspected cases of seasonal pasture myopathy this fall in Minnesota and feel it is an under-diagnosed condition in North America,” said lead researcher Dr. Stephanie Valberg of the University of Minnesota. “Our goal is to work with horse owners to identify which horses are at risk and find the best diagnostic test for this condition.”

The research team need to build up a database of information on cases of the SPM, so that they can start to work out / identify the common risk factors. They hope to be able then to make suggestions of management changes to reduce the risk of the disease condition

If you suspect your horses has (or had) SPM, Dr Valberg's research team would like to hear from you. The first step is to complete a short questionnaire to see if your horse has the condition.

For more details about Seasonal Pasture Myopathy, and details of how you can help research into the condition, go to the University of Minnesota Equine Center website:

http://www.cvm.umn.edu/umec/SPM/home.html

Ancient artists spot on

Ancient cave paintings probably give an accurate portrayal of the horses that roamed the earth at the time, according to new research.

For years, archaeologists have debated whether cave paintings were intended as a realistic portrayal of life as seen by the artist, or whether they were a flight of fancy, having symbolic significance. The latter view was fuelled by the fact that, although genes for bay and black hair colour had been identified in ancient DNA, the gene for spotted coat colouring had not been found.

Now a multicentre research project has found the gene responsible for leopard spotted coat colouration in DNA from prehistoric horses.

The international team of researchers has found that all the colour variations seen in Palaeolithic cave paintings – including distinctive ‘leopard’ spotting - existed in pre-domestic horse populations, lending weight to the argument that the artists were reflecting their natural environment.

Professor Michi Hofreiter, from the Department of Biology at the University of York, said “...our results suggest that, at least for wild horses, Palaeolithic cave paintings, including the remarkable depictions of spotted horses, were closely rooted in the real-life appearance of animals. 

“While previous DNA studies have produced evidence for bay and black horses, our study has demonstrated that the leopard complex spotting phenotype was also already present in ancient horses and was accurately depicted by their human contemporaries nearly 25,000 years ago. 

“Our findings lend support to hypotheses that argue that cave paintings constitute reflections of the natural environment of humans at the time and may contain less of a symbolic or transcendental connotation than often assumed.”

Read more at equinescienceupdate.com