Grant: Operating Grant

Postural Tachycardia Syndrome (POTS) is a chronically disabling disorder of autonomic nervous system function ("dysautonomia") with cardiovascular dysregulation, yet their causes remain largely unexplained. POTS is characterized by an excessive increase in heart rate on standing, and characteristic symptoms on standing that are relieved by lying down, including palpitation, chest pains, tremulousness, blurred vision and mental clouding. POTS affects up to 0.33% of the population, mainly women of childbearing age. Patients have very poor health-related quality of life (comparable to heart failure). The mainstay of pharmacological therapy for POTS includes Beta-blockers (e.g. propranolol) to control the excessive heart rate, and midodrine, a vasoconstrictor. It has long been suspected that POTS may be an autoimmune disease, but this has been hard to prove. We recently found that the blood of some POTS patients has antibody activity against "adrenaline receptors" that regulate heart rate and blood vessel tone. This is a newly discovered pathophysiological mechanism in POTS that could explain the symptoms in this disorder. We propose a series of translational studies with the ultimate goal of personalized medical treatment for POTS patients. We will build on the preliminary work and assess the physiological significance of these antibodies in POTS patients. By using pharmacological drug "probes", we will determine if these antibodies affect POTS patients' responses to commonly used drugs. These innovative aims could bring an antibody guided, personalized medicine approach to the management of POTS patients. We will also test "proof of the concept" that clearing these antibodies will reverse the pathophysiology in ("cure") POTS patients. Taken together, these highly innovative translational studies could create novel treatments for patients with POTS.