LSU reports on horse study over pergolide approval

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Pergolide has been found to control PPID in horses.
Pergolide has been found to control PPID in horses.

“La Veterinaire”, the News-Magazine of the Louisiana State University School of Veterinary Medicine, reports on the work of  Professor Frank Andrews, including an important study which showed pergolide as a suitable treatment for equine Cushing’s disease.

Researchers at Lousiana State University’s School of Veterinary Medicine often partner with industry in the search for new treatments for animal and human diseases.

Dr Frank Andrews, professor of veterinary medicine and director of the Equine Health Studies Program, brings experience and expertise to corporate/academic partnerships to develop new treatments for horses.

In a recent study funded by Boehringer Ingelheim Vetmedica, Inc (BVIM), Dr Andrews participated in research to develop the drug pergolide to treat one of the most common conditions of horses older than 15 years, equine Cushing’s disease, otherwise known as pituitary pars intermedia dysfunction (PPID).

Horses with PPID exhibit hirsutism (long, curly hair coats that do not shed properly), increased water consumption, lethargy, muscle wasting, laminitis, and secondary infections, including sole abscesses, tooth root infections, and sinusitis.

The pituitary gland, at the base of the brain, normally produces a wide array of important hormones that regulate organ functions.

In PPID, the middle lobe of the pituitary gland (pars intermedia) becomes enlarged and overproduces cortisol. In healthy horses, cortisol production is inhibited by dopamine so that release of the hormone is tightly controlled. Horses with PPID do not seem to produce dopamine in adequate levels so that cortisol release continues unabated without regulation.

In this sense, lack of dopamine production in PPID is analogous to the diminished dopamine availability observed in human Parkinson’s disease; however, because a different part of the brain is involved, the resulting disease is quite different.

The clinical trial undertaken by Dr Andrews in collaboration with researchers at Michigan State University and Oklahoma State University, in a multicenter effort, demonstrated that the clinical signs of PPID can be controlled by administration of pergolide, which apparently acts as a dopaminergic agent inhibiting excessive cortical production from the pars intermedia of the pituitary gland.

Horses in the study showed improved hair coat, more complete and timely shedding, increased muscle mass, and a better mental attitude.

In addition, there was less risk of developing laminitis and infections, such as sinusitis, pneumonia, and tooth root abscesses.

These studies resulted in pergolide being accepted as the first Food & Drug Administration-approved drug for treatment of PPID in horses.

Dr Andrews also assisted BVIM in developing a website to educate clients and veterinarians about PPID (http://www.prascend.com).

Dr Andrews has performed many studies on the pathogenesis, treatment, and prevention of equine gastric ulcer syndrome (EGUS). The anatomy of the equine stomach makes it uniquely predisposed to the formation of mucosal ulcers, which leads to poor performance, colic (abdominal pain), roughened hair coat, lack of appetite, and weight loss, a real problem in both weanling and performance horses.

Recently there has been considerable interest in the use of plants, herbs, minerals and natural agents offered as feed supplements to prevent EGUS and gastric ulceration in humans.

Using a model where he can assess the impact of supplements on gastric mucosal integrity, Dr Andrews is currently investigating the efficacy of several feed supplements to prevent EGUS, including an extract of Seabuckthorn berries (Hippophae rhamnoides) and a combination of performance minerals and a gut-conditioning agent. Initial studies of this latter product appear promising for the prevention of EGUS after initial treatment.

To better understand gastrointestinal function, Dr Andrews has been using a wireless capsuled gastrointestinal monitoring system that measures pH, temperature, pressure, and transit time after it is swallowed. As the capsule passes through the gastrointestinal tract, it transmits data to a monitor attached to the patient. This allows an accurate and non-invasive estimation of gastric emptying time (the time required for food to pass through the stomach) and transit time through the rest of the gastrointestinal tract.

Dr Andrews found that the adult horse empties the stomach in about eight hours and it takes about 48 hours for material to traverse the entire 140 feet of a horse’s intestines. Dr Andrews believes that such a non-invasive model will allow him to assess the impact of medications on gastrointestinal function and assist in the diagnosis of diseases of the stomach and intestines that alter motility, such as duodenal strictures (narrowing) and colic.

“By building relationships with industry, academic research institutions, such as LSU, can put into practice and explore the feasibility of cutting-edge technology and innovative medicines to diagnose and treat diseases affecting horses and other animals,” Dr Andrews said.

 

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