Parathyroid Allotransplant for Treatment of Hypoparathyroidism

PROJECT SUMMARY/ABSTRACT Chronic hypoparathyroidism (hypoPT) is a rare, debilitating disorder defined by low serum calcium and parathyroid hormone (PTH) levels that are low or fail to respond to the degree of hypocalcemia. Symptoms of hypoPT range from perioral or distal extremity numbness and tingling to muscle cramping, tetany; and in severe cases, seizures, cardiac arrhythmias, laryngospasm and bronchospasm. Unlike many endocrine disorders where treatment focuses on replacing the deficient hormone, treatment for hypoPT relies on oral calcium and activated vitamin D (calcitriol) supplementation. Large doses of oral calcium are often difficult to tolerate and often inadequately control hypocalcemia. A delicate balancing effort between the control of symptomatic hypocalcemia and excessive calcium replacement is needed to avoid formation of kidney stones or calcifications in tissues, such as the basal ganglia. In addition, conventional treatment does not address hyperphosphatemia. The goal of this proposal is to provide parathyroid cell replacement via parathyroid gland (PTG) allo- transplantation to provide the missing hormone, and to effectively replace the missing regulatory system. Parathyroid autotransplant into the intramuscular space of the forearm is a well-established strategy that can provide the essential autoregulation of PTH to maintain calcium and phosphorus homeostasis and has been used for decades in patients who have had extensive parathyroid surgery to treat severe hyperparathyroidism. Allotransplantation of normal parathyroid glands from deceased donors has never been studied in a prospective trial. Our objective is to test the hypothesis that PTG allotransplantation, using normal PTGs from deceased donors, is safe, allows PTG engraftment, and obviates the need for conventional therapy or PTH replacement for people suffering from hypoparathyroidism. In order to accomplish this objective, we are proposing a pilot trial with specific aims to investigate the efficacy of PTG transplantation (Aim 1) and the safety of the transplant procedure and associated immunosuppression (Aim 2).