Beta-Aminoproprionitrile Fumarate (BAPN)
In April of 1993, Ohio's 1992 Champion Sprinter Onion Roll suffered a catastrophic bowed tendon. The injury was so painful for the horse that Onion Roll's owners, Ed and Wendy Cash, were brokenheartedly considering euthanasia. About that time, the Cashes heard about an experimental drug and rehabilitation program being tested on horses suffering from bowed tendons. Believing Onion Roll deserved a second chance, the Cashes enrolled their gelding in the experimental program in the hope of saving the horse's life. After undergoing about five months of treatment and rehabilitation, Onion Roll returned to racing to win a $4,400 claiming race going two furlongs at Thistledown. More notable than the win was the fact that Onion Roll's time of :2045 equaled the Thoroughbred world record for that distance.
The experimental drug Onion Roll received was beta aminopropionitrile fumarate, nicknamed BAPN. After more than five years of study, BAPN is in the final stage of the FDA's approval process for new drugs. FDA-regulated field trials for BAPN are currently underway at various sites across the country, including the University of Pennsylvania, Michigan State, The Ohio State, Virginia, and Texas A&M. The trials are expected to be completed late this year, and BAPN supporters expect the drug to be available in 1997.
"I expect it (BAPN) will be approved (for horses) more rapidly because it's classified as a breakthrough drug and given expedited review status," said Bill Davis, MD, an Arizona-based vascular surgeon who helped pioneer early studies of BAPN on humans. "It's on the fast track because there is no other pharmacological treatment for a ruptured (bowed) tendon."
Most bowed tendons are athletic related and come in a wide range of severity. Bowed tendons are the most common injury suffered by Thoroughbred, Quarter Horse, and Standardbred racehorses. Sport horses like polo ponies, hunters and jumpers, and dressage and steeplechase competitors are also prone to bows.
A bowed tendon occurs when a horse ruptures the superficial flexor tendon of a foreleg, just behind the cannon bone. The term "bowed tendon" comes from the appearance of the tendon while injured and after healing. The development and buildup of scar tissue in a net-like woven pattern causes the bowed appearance. Normal healthy tendon fibrils (slender fibers) run parallel, have a leaner appearance, and are more flexible. Once a tendon ruptures, the ensuing cross-linking and buildup of scar tissue causes tendon shortening, restricts tendon flexibility, and increases the chance of re-injury.
The most popular tendon repair methods used today are tendon splitting, check ligament desmotomy, external blistering, extensive rest, controlled exercise, and in some cases, pin firing. These procedures, however, contribute to the buildup of randomly cross-linked scar tissue. BAPN, on the other hand, inhibits initial cross-linking between collagen fibrils, allowing greater tendon lengthening, restoration of the gliding function, and parallel scar fiber alignment resulting in greater flexibility and resistance to strain.
"Our goal is to try and give injured horses a better repair by enhancing the repair so the scar lines up in a more parallel direction from top to bottom," said Ron Genovese, DVM, who has been working closely with Davis on the equine portion of the BAPN project since 1991. "We want the tendon to be functional enough to return the horse to competition."
Genovese's private practice is based in Cleveland, Ohio, and is limited to race and sport horses. Since partnering with Davis, Genovese has treated 55-60 horses during his clinical research on BAPN. Genovese was instrumental in developing the dosage, toxicity, and rehabilitation guidelines that are currently being used in the FDA's field trials on BAPN. Those guidelines include waiting about 30 days for the injury's acute inflammation to subside before administering the first series of BAPN injections.
Davis said it takes about a month for the horse's body to overcome the injury's initial trauma and to begin producing scar tissue to repair the tendon lesions. Once the scar tissue begins forming, the BAPN injections block the cross linking of the new scar tissue. Coupled with a rigid and controlled exercise program, new fibers can align in a parallel fashion rather than a random fashion.
The BAPN treatment involves injecting about one-tenth of a cc of the drug into each linear centimeter of the injured tendon in about 50 sites every other day for 10 days--a total of five treatments. Following the injections, the horse is initially confined to a stall and walked for two months.
"This is not a program where you just stick the drug in and walk away," Davis said. "We never turn a horse out before four or five months and rarely put a horse back in training before six months."
Horses suffering slight tendon injuries remain on the restricted exercise program for about six months. Moderate injuries require about nine or 10 months of rehabilitation, and serious injuries take a year or more. Rehabilitation involves gradually increasing the exercise load while monitoring the tendon with ultrasound until the tendon reaches full range of motion without sonographic regression.
"Our intent is not to reduce recovery time," Davis said. "Tendon injuries should not be treated by the impatient."
Virginia Reef, DVM, director of large animal ultrasound and cardiology at the University of Pennsylvania's New Bolton Center, agrees with Genovese that BAPN will not speed up recovery. Reef also has been instrumental in the BAPN research and has treated about 150 horses since 1993.
"This is not a quick fix," said Reef, whose patients include many more performance and sport horses, including dressage, combined training, and timber competitors. "There will be some owners and trainers who won't want to give a horse the time it needs with this treatment. BAPN is for those individuals who want to do the best for the horse in terms of quality repair regardless of how long it takes."
Keys To Success
According to Davis and Genovese, the keys to BAPN's success are proper administration of the drug, time, and a regimented rehabilitation program that includes a systematic series of ultrasound examinations. The use of diagnostic sonographics (ultrasound readings) allows the attending veterinarian to monitor the collagen remodeling of scar tissue and the tendon's response to loading.
"Prior to the introduction of diagnostic ultrasound in the 1980s, there was no practical imaging way to accurately evaluate the extent of a tendon injury or to monitor repair," Genovese said. "Ultrasound allows us to see what is going on with the injury, to make a more accurate diagnosis, and to monitor the healing process."
Sonographic monitoring of the injured area allows a veterinarian to better determine a tendon's stress capacity during the rehabilitation process and to know when the tendon is ready to bear the increasing load as a horse moves from trotting to cantering to galloping to racing. This monitoring is key to BAPN's success, but also one of Davis' and Genovese's greatest concerns.
"Vet supervision and sonographic monitoring is essential," Genovese explained. "It is not unusual for owners and trainers to think a tendon is stronger than it really is and to make exercise movement mistakes. Failure to determine proper load capacities can result in a low-grade re-injury that can set the horse back to zero."
Case In Point
Although there are many factors that can affect the final results of BAPN treatments--training techniques, race and event selection, other injuries--Davis and Genovese are optimistic about its potential. They claim that in some cases, BAPN can return a horse to the level at which it was competing prior to injury.
At the time of his injury, Onion Roll was seven years old and racing on the Ohio circuit, jumping between allowance and upper-level claiming races. The last race before his injury was at Thistledown, in a $16,000 claiming race, which he won. Prior to that, he won a five-furlong allowance race at Thistledown. After five BAPN treatments and about 5 1/2 months of rehabilitation, Genovese determined that Onion Roll was ready to return to racing. Not wanting to overtax the gelding in his first race back, Onion Roll's connections dropped the gelding into a claiming race for a $4,000 tag at Thistledown--the race in which he equaled the world record for two furlongs.
Following his triumphant return, Onion Roll's connections jumped the gelding into allowance company, where he won again. He finished second in his next race, competing in allowance company. Over the next two years, Onion Roll flip-flopped between allowance company and claiming events, winning seven more races and earning more than $30,000. In the course of his career, Onion Roll raced 65 times, won 28 races, finished second 14 times, and amassed $206,106 in earnings.
"The Cashes were justly rewarded for their patience," Genovese said. "Their willingness to try a new approach not only benefited their horse, but other tendon injured horses."
In hindsight, Genovese believes Onion Roll might have been able to perform even better had the horse had a longer rehabilitation. Onion Roll came along early in Genovese's research, and the practitioner had not yet determined optimum dosage or rehabilitation parameters.
"When we started, we had nothing to go on," Genovese recalled. "We went through quite a few horses before we were able to categorize tendon injuries by severity--slight, moderate, or severe--and the best way to treat and rehabilitate those injuries."
One of Genovese's most significant findings was that even slight tendon injuries required a minimum of six months rest. Putting a horse back in training before six months greatly reduced the horse's chance of returning to competition while increasing the chance of re-injury. Onion Roll returned to racing in less than six months.
"In our first phase of 25 horses, we attempted to put those horses back in training in less than six months," Genovese said. "We experienced a significant failure rate in that phase. However, in the second phase of 30 horses, we kept them out of training longer and experienced a significantly higher success rate."
Although some horses never made it back to racing or competition, Genovese said most of the horses did recover to the point they could participate in less-strenuous activities. Reef said she has had tremendous success returning horses to competition.
"Many horses in this program made it back to competition," she said, "horses that would never have made it back to racing or showing had more traditional tendon repair procedures been used to treat their tendon injuries."
Although dosage, toxicity, and rehabilitation parameters have been determined, cost for the BAPN treatments and ensuing rehabilitation program have not been determined. Genovese feels strongly, however, that the cost of the injections, ultrasound, and veterinary monitoring should be packaged under one fee. The one-fee concept is to ensure that sonograms are done as outlined in the rehabilitation schedule and to ensure a greater chance of recovery.
Although the BAPN studies and FDA trials are targeting injuries of the superficial flexor tendon (the common "bowed tendon"), Reef is confident BAPN can be used to enhance repair and recovery in any tendon or ligament injury. She said it works very well when used to treat tendon lacerations, claiming BAPN only allows minimal, if any, adhesion of scar tissue. Once BAPN is available, all three practitioners expect it to be well accepted by the equine community.
"Everyone who has worked, or had some experience, with this drug is very excited about its potential and can't wait for it to be approved," Reef said. "Once a trainer or owner has one horse treated and sees the result, he is quick to bring the next bowed horse."
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