Pergolide Study

Investigation of genetic component of pergolide efficacy & adverse effects in horses undergoing treatment for pituitary pars intermedia dysfunction (PPID)

Equine pituitary pars intermedia dysfunction (PPID), previously known as equine Cushing’s, is a common disease affecting older horses. This condition results when the neurons of the hypothalamus are damaged and lose their inhibition/control of the cells of the pars intermedia of the pituitary gland.1 There is no cure for this condition and treatment is aimed at slowing progression and controlling the signs in affected horses.  The only FDA approved drug for treatment of PPID in horses is PrascendThe active ingredient of Prascend is pergolide, a dopamine receptor agonist, which counteracts the loss of dopamine in the neurons of the hypothalamus.  Pergolide is the most common medication used in horses.  This drug was originally used to treat Parkinson’s disease in humans (Figure 1).2 

 Pergolide medicine

 

Figure 1. The FDA approved pergolide for horses manufactured by Boehringer Ingelheim as Prascend.

 

 

It is well known that PPID horses can respond differently to treatment with pergolide.  Various reports show an average of 60-80% treatment success.3-4 However, these reports can be difficult to interpret as studies classify success quite differently. Another complicating factor is the high number of adverse effects. Some of the most common include anorexia, colic, weight loss, and a change in behavior/attitude.  Anorexia has been reported in up to 32% of horses on pergolide in some studies.5

These adverse effects can be a large problem when treating affected horses and lead veterinarians or owners to reduce or stop pergolide treatment.  Resulting in clinical signs to return or worsen, and the disease to progress. It is well established that genetics can contribute to an individual's response to a specific medication and there are many known examples of genetics affecting medication choice or dose in human medicine.6

​​The goal of this project is to identify genetic alleles (or mutations) that may contribute to differences in responses to pergolide treatment or result in adverse effects. If genetic differences are identified, differences in treatment may be needed. For example, animals unlikely to respond may need a higher dose or animals likely to have adverse effects may need a lower dose. 

HOW YOU CAN HELP

In order to complete this important research, we need your help enrolling the appropriate horses to study. We are looking for horses that meet the following criteria:

1. Over the age of 15 at time of PPID diagnosis
2. Diagnosis made by veterinarian and diagnosis included bloodwork
3. Horse has/had clinical signs consistent with PPID (long shaggy haircoat, muscle atrophy, changes in mentation, or recurrent infections)
4. Horse has been on pergolide therapy for a minimum of 6 months and has had recheck blood values (including ACTH, TRH stim, or dexamethasone suppression blood work)

If your horse fits this criterion, please consider contributing to equine research by enrolling in our study. We cannot do this without you and your horses! We are happy to discuss any questions regarding eligibility- please contact eggl-ppidstudy@umn.edu.  

PPID Research Team:

Dr. Molly McCue (PI, University of Minnesota)
Dr. Dianne McFarlane (Co-I, University of Florida)
Dr. Lauren Hughes (PhD Student, University of Minnesota)

If you have any questions, please contact the research team at eggl-ppidstudy@umn.edu.

*This project has received funding by the University of Minnesota and the American Association of Equine Practitioners Foundation for the Horse.

Sources

Sources

  1. D. McFarlane, Pathophysiology and clinical features of pituitary pars intermedia dysfunction: Pathophysiology of PPID. Equine Veterinary Education, vol. 26, no. 11, pp. 592–598, Nov. 2014, doi: 10.1111/eve.12237.
  2. J. S. Fortin et al., Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction, BMC Vet Res, vol. 16, no. 1, p. 356, Dec. 2020, doi: 10.1186/s12917-020-02565-3.
  3. R. C. Tatum, C. M. McGowan, and J. L. Ireland, Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review, The Veterinary Journal, vol. 266, p. 105562, Dec. 2020, doi: 10.1016/j.tvjl.2020.105562.
  4. N. Hague, A. E. Durham, and N. J. Menzies‐Gow, “Pergolide dosing compliance and factors affecting the laboratory control of equine pituitary pars intermedia dysfunction,” Vet. rec., Mar. 2021, doi: 10.1002/vetr.142.
  5. A. M. Wright, “Pharmacokinetics of pergolide in normal mares," 2009. Kansas State University. p. 55.
  6. “Pharmacokinetics and Pharmacodynamics of Oral Pergolide Mesylate In Horses With Pituitary Pars Intermedia Dysfunction,” Equine Vet J, vol. 49, pp. 25–25, Sep. 2017, doi: 10.1111/evj.46_12732.
  7. Boehringer Ingelheim. Prascend Package Insert. Revised 3/2020. https://prascend.com/sites/prascend_global/files/PRASCEND-PI.pdf
  8. D. T. Wake, N. Ilbawi, H. M. Dunnenberger, and P. J. Hulick, “Pharmacogenomics,” Medical Clinics of North America, vol. 103, no. 6, pp. 977–990, Nov. 2019, doi: 10.1016/j.mcna.2019.07.002.