Laminitis: what new research is telling us

March 29, 2007

This report outlines recent research into laminitis. It is in no way intended to suggest any course of treatment for cases of the disease. Laminitis is a serious and potentially fatal problem. Consult your veterinarian as early as possible.

Millions of dollars being spent on research is taking us ever closer to a complete understanding of laminitis, and ways to control the disease. Neil Clarkson reports.

The forces are gathering in the war against laminitis.

Where there is a will, there is a research dollar, and more money than ever is being directed toward finding effective treatments for the disease.

The death of Kentucky Derby winner Barbaro brought sharply into focus the challenges that laminitis, or founder, bring. The champion racehorse survived and recovered from a catastrophic leg injury, only to succumb to laminitis.

Barbaro's battle with laminitis raised awareness of the problem, and has re-energised efforts to find solutions.

In any war, the first rule is to know your enemy.

In recent years, fresh research and advances in technology have enabled us to understand the process in much greater detail.

At a basic level, we know that laminitis is an inflammation of the delicate layers beneath the hoof wall, called laminae. It causes severe pain and, if not arrested or reversed quickly, can cause permanent and painful changes in the foot that leave little option but to euthanize the animal in some cases.

We know that ponies and overweight horses are more prone to the disorder. We know that an excess of carbohydrate during strong spring growth, and the resulting fermentation in the hind gut, can trigger bouts. Mechanical overload of a sound leg is another common cause, as is drinking too much cold water after exercise.

The nature of the inflammation in a hoof has been straightforward to study. Scientists also have a clear understanding of the way in which damage progresses in a foot.

On the surface, it would seem that laminitis should not present such a serious test to veterinary science. The challenge arises because researchers have yet to understand all aspects of the mechanism by which the condition arises.

Indeed, the Australian Equine Laminitis Research Unit has worded its mission statement thus: To discover the mechanism of laminitis and make it a preventable disease.

Without an understanding of this mechanism, it is proving very difficult to develop any effective form of medical intervention that that can prevent or cure the disease.

Laminitis is clearly a dynamic condition, that ebbs and flows with a raft of biological processes going on within a horse.

Researchers believe that some parts of the laminitis problem involve normal biological processes unfolding at the wrong time, or in the wrong place.

Pinning these down is just one aspect of the challenge researchers face.

Part of the battle is being waged at a genetic and cellular level.

Scientists believe that a greater understanding of the enzymes of the laminae region will prove important in finding a solution. Such knowledge would provide a greater understanding of what genetic controls exist between the hoof wall and the laminae.

Once these processes are understood, researchers can only then look towards factors that might influence them, they argue.

The complexities and function of the hoof also require further research and understanding.

We all know, for example, that the hard hoof wall grows down from the coronet.

However, cells in the adjoining laminae don't grow at nearly the same rate, meaning there is an enzyme-driven mechanism by which the laminae must continually detach and then re-attach itself to allow the hoof wall to grow down properly.

The mechanism must be effective, for the hoof wall can grow at up to 20 times the rate of the laminae.

This process has been likened to two pieces of Velcro being unfastened and then reattached, with one of the pieces gradually working its way down.

Could problems or interference with this biological process be an important factor in laminitis? If so, what triggers make this process go wrong?

Scientists already know that that a protein called laminin-5 is damaged in some way in laminitis, resulting in a failure of this bond. Once this bond is weakened sufficiently, the weight of the horse alone can be enough to cause tearing and inflammation of the laminae/hoof bond, and potential rotation of the coffin bone.

It seems clear that more horses could be saved in severe cases of laminitis if some means of weight-bearing mechanical support could be introduced as soon as possible, such as a sling hung from a stable roof.

What else do we know?

Scientists understand that fructans in pasture play a big part in laminitis. These fructans cause fermentation in the hind gut (large intestine).

Fructans are chain molecules that represent a significant part of a plant's reserve of carbohydrates. Fructan levels tend to be higher in stressed plants. Under some conditions, fructans can represent up to half of grass's dry-matter content.

While horses enjoy eating them, they do not get digested in the small intestine. They continue through the digestive system, instead being fermented by bacteria in the hind gut. The hind gut becomes more acidic, resulting in a surge in the population of streptococcus bacteria, which overwhelm the normal population of enterobacter bacteria.

Once the process is under way, numbers of streptococcal bacteria can double every 12 hours.

Some researchers believe the big streptococcal population damages the gut lining, and toxins from the bacteria then have an opportunity to escape into the bloodstream, travelling to the hooves and triggering laminitis, probably by activating enzymes whose normal function is to detach the laminae from the hoof wall.

Thus the need to control horse grazing when fructan levels are high.

Studies also show that chilling affected tissues will slow the advance of laminitis, providing a possible opportunity to get the problem under control before lasting damage results.

It is thought this works by slowing the metabolism in the chilled tissues. It also reduces blood flow to the hoof, possibly reducing the inflow of any toxins. However, there are potentially serious problems surrounding any therapy based around this principle.

For a start, part of the problem with laminitis is a lack of blood to affected tissues, causing them to die. Reducing this blood supply even further at a crucial time could have disastrous consequences.

Secondly, severe and prolonged restriction of blood to the hoof through extreme cold can result in a total failure of the bond between the hoof-wall and the laminae once blood flow is restored, resulting in the entire hoof wall being shed.

Other research points to a poor uptake of glucose by hoof cells playing a part in the laminitis equation.

Cell uptake is known to be reduced in cases of obesity, cushings disease, a poor oxygen supply, or high levels of fats in a horse's blood plasma. The uptake mechanism is also known to be affected by blood infection, or toxins in the blood (hence the laminitis link to fermentation in the hind gut).

An effective treatment for laminitis may one day involve a medication or strategy that encourages hoof cells to increase their glucose uptake.

There is no doubt that the knowledge of laminitis being gained at a molecular level is pushing science closer to more effective cures or control measures.

Further research, in the United States, is looking at the role of blood vessels in the disease.

Scientists from the University of Georgia are evaluating how blood vessels in the hoof change with the disease.

Problems with blood vessels in the foot have long been known to play a part in laminitis, with more recent work pointing to the difficulty being with veins, not arteries.

The passing of calcium ions through the wall of veins in the laminae has been shown to cause constriction, particularly in smaller vessels. Interestingly, this sensitivity appears confined only to the laminae area.

It has already been shown that the walls of the smaller veins become tighter in laminitis. It is probably one of the first responses in a hoof to whatever has triggered the bout of laminitis.

The promise is clear: If researchers can find the precise mechanism that causes constriction of the smaller veins in the laminae, a treatment might be found that prevents constriction and thus prevents laminitis altogether.

Constriction of the blood vessels is a double whammy for a horse, as the inflammation resulting from laminitis will, by itself, cause a further reduction of blood flow in the hoof. Where there is no blood, the tissue will die.

Yet another avenue of research proposes that, with any weakening of the laminae, the foot becomes unbalanced because it is unable to cope with the pull of the deep digital flexor tendon.

This creates a stretching of the laminae, resulting in tension which squeezes blood out of the laminae tissues. A laminae under such continuous load can be starved of blood and eventually start dying.

This proposition elegantly explains why a horse is prone to laminitis in a leg forced to bear additional weight because of an injury to another leg.

It challenges conventional wisdom that a horse with a leg problem is best standing still and resting the injury. An injured horse that is moving around is stimulating blood flow to the hooves, arguably lessening the risk of laminitis.

Veterinarians who specialise in laminitis problems are clear about one thing: protecting sound feet must be a priority as soon as any leg injury occurs. Once the outward symptoms of laminitis appear, chances are that the problem has been developing for some weeks.

In Barbaro's case, even the best of care was unable to save him from chronic laminitis.

And so the puzzle slowly but surely comes together. Every laminitis researcher will acknowledge that their role centres on putting more pieces of the jigsaw in place, with the eventual promise of effective treatments and preventative measures.

A number of foundations around the world are actively funding laminitis research. Funding is coming from the United States Department of Agriculture, the Morris Animal Foundation, the Grayson-Jockey Club Research Foundation, and the White Fox Farm Foundation.

The recently created Barbaro Memorial Fund is pledging its considerable resources to the fight. The research projects it will fund will focus on laminitis.

The National Thoroughbred Racing Association is also organising fundraising to pay for laminitis research.

The push for answers has gathered considerable momentum.

While researchers know much more about laminitis than they did even a few years ago, the fact remains that it remains a debilitating disease; and survival of a horse is far from guaranteed, even after the best of care.