Dr. Lawrence R. Soma, Dr. Cornelius Uboh and Dr. Mary Robinson, researchers from the laboratories which made the major breakthrough in regard to the presence of EPO in racehorses, have turned their attention to a currently-untestable drug which has been rumoured to have found its way into the standardbred racing industry

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"At this point it's just rumours," Dr. Soma told Trot Insider. "It's (the rumours have) been from a lot of people – breeders, owners and horsemen. The implications seem to be more in the standardbred industry, but someone from the thoroughbred industry asked me about this drug this morning."

Although Dr. Soma confirmed that use of the drug in the industry has been based purely on speculation to this point, he did present a logical, pro-active position as to why the industry – if it wants racing to be on the level – should be financially supporting the testing of it right now.

"Whether or not it (the drug) is currently in the industry, if this drug eventually becomes available, you know it is going to be in the industry, so you might as well get a jump start on this stuff," Dr. Soma said. "We're (the horse racing's industry’s regulatory bodies are) always behind the eight-ball. If this drug is going to be beneficial in the human field, and will eventually be a commercial product, you know it's going to be used (in the racing industry), so you might as well get a jump start on it right away."

Dr. Soma and Dr. Robinson work in collaboration with Dr. Cornelius Uboh, director of the Pennsylvania Equine Toxicology and Research Laboratory, which is located at the University of Pennsylvania School of Veterinary Medicine. The facility has made its presence felt in the horse racing industry – particularly in the last few years, as it is where “the EPO riddle” was solved, according to Dr. Soma.

And as Dr. Soma explained to Trot Insider, they are looking to solve another riddle: the detection of Myo-inositol-trispyrophosphate, better known as ITPP, in equine.

Dr. Soma and Dr. Robinson explained that ITPP was formulated in France in 2005 and that it is being developed for legal use in humans for multiple diseases. The doctors told Trot Insider that the drug is thought to cause hemoglobin to release oxygen into the tissues at a higher rate. Therefore, if used within endurance sports, ITPP would act as a performance enhancer.

"The mechanism of how it actually works has not been really well defined,” Dr. Robinson explained. “The theory is that it binds to hemoglobin and causes the hemoglobin to release oxygen more efficiently in the tissues, but it's still a theory.” Dr. Soma added that ITPP has a unique action and that it is probably confined to the red blood cell. “We're not sure because we haven't looked at it,” he said.

Although EPO leads to increased amounts of hemoglobin in the system, ITPP modifies the hemoglobin in the red blood cell to release more oxygen as the RBC enters tissues which require oxygen. Both doctors explained that the two drugs are "totally different.” They each stated that EPO is a large, protein-based drug which weighs about 130 Daltons, while ITPP is a standard compound drug which has a small molecular weight.

After having been told by multiple horse racing sources that ITPP is being used within the industry, Dr. Soma said he and Dr. Robinson started to research ITPP. "We began to review the literature, and there is 'science' in mice, and there is some 'science' in humans about the potential medical benefits of this compound," Dr. Soma explained. Dr. Robinson said that so far (in terms of public literature) ITPP has only been administered to mice. “No studies with humans have been published yet,” she explained. “It is currently in Phase 1 clinical trials, which means that they are not necessarily looking for an effect, but just to make sure that it is safe to administer."

The pair of doctors explained to Trot Insider that they have submitted an abstract of a proposal to research the drug. "This drug may not be difficult to synthesize, but we are not sure," said Dr. Soma. The duo did explain that funding will be needed in order for the testing to go to the next level.

"What we have submitted so far is an abstract. An abstract is a brief overview of the whole plan. It's a preliminary step," Dr. Robinson explained. "On the project side of things, this compound is not commercially available. The only people that have it are the researchers who are using it. So, we have already contacted them to see if they would be interested in providing us with some of the compound so we can use it to develop a method to test for it. That is where we are in terms of the project."

Dr. Robinson explained that the initial paper which showed the synthesis of ITPP was in 2005, so the drug couldn't have been used in the industry before 2005. "The paper that actually showed that it enhances performance didn't come out until 2009," she explained. "If it is being used to enhance performance, I don't think people even knew that it could enhance performance before 2009."

AICAR

The two doctors are also currently researching another performance-enhancing drug rumoured to be used in the racing industry. They heard about the rumoured use of AICAR (aminoimidazole carboxamide ribonucleoside) at the same time they were tipped off about the purported use of ITPP.

"The reason we started on the AICAR first is because it is commercially available from multiple sources," said Dr. Robinson, who explained that AICAR is referred to by some as 'the exercise pill.' "It has been shown to be safe; there is kinetics data on it in humans; it is already in Phase III clinical trials, which means they (researchers) are looking for an effect. It had a good effect in Phase II trials, so they are now increasing their numbers before they try to have it approved by the FDA (Food and Drug Administration)."

Dr. Robinson explained that AICAR is a completely different mechanism than that of ITPP.

"We are investigating several mechanisms by which AICAR may enhance racehorse performance. One possibility is that it goes into muscle cells and changes gene expression. It has been shown to activate a protein called AMPK, which is normally 'up-regulated' (or activated) when people exercise. AMPK regulates how the cell uses glucose and fatty acids, the fuel sources needed for contraction. When scientists looked at gene expression in mice treated with AICAR, they found that it essentially causes the same effect as exercise. And it has been found in mice that if you give this drug to them without any sort of training it will enhance their endurance on a treadmill. Research has shown that the mice will run further and faster after receiving the drug for four weeks. Whether this is also true for very fit race horses, and whether it will speed up training, is not known. AICAR can also increase blood flow and glucose delivery to the muscle immediately after being given. Whether the performance enhancing effects seen in the mice were due to changes in gene expression, or due to these short term effects is also not known."

She went on to explain that AICAR is naturally produced by both people and horses' bodies, and since there is normally a certain amount of AICAR in the body it makes it a challenge to detect when 'the exercise pill' has been utilized.

"When you are trying to detect whether or not someone is using it, you have to know what 'normal' is first," Dr. Robinson explained. "We are pretty-well underway with this project. We have already obtained funding to start the study from the RMTC. We have collected over 100 blood samples from horses – racing horses and resting horses – and it is underway." Dr. Robinson is partially supported on an RMTC fellowship program awarded to highly trained promising scientists.

When asked whether the use of AICAR has a detrimental effect on equine, Dr. Robinson said she was unsure at this time. "The AICAR is the same molecule in humans, horses and mice. Because it is the exact same molecule, I do not expect it to have a negative effect on a horse. It has actually been shown to be extremely safe in humans. Very large doses have been used and have not had any side effects at all."