Treatment of Hypoparathyroidism with Parathyroid Hormone

描述（由申请人提供）： 甲状旁腺功能减退症是一种罕见的疾病，其中甲状旁腺激素（PTH）显着减少或缺乏循环。这是为数不多的剩余的激素缺乏症的状态之一，其中与失踪的激素替代迄今为止已经不可用。如果没有PTH，患者的钙稳态异常，表现为低钙血症和高尿钙排泄。目前主要的治疗方法是钙和维生素D。然而，这种方法具有重要的临床局限性。所需的大剂量钙和维生素D与高钙血症、高钙尿症和维生素D毒性的风险相关。这种方法也不能纠正由于缺乏PTH而导致的骨骼缺陷。由于甲状旁腺功能减退症是一种罕见疾病，研究人员和资助机构都不愿意支持PTH作为一种治疗方法的发展。在人们可能考虑的甲状旁腺激素分子中，最近开发的重组人PTH（1-84）是最有吸引力的，因为它是天然激素，正是这些个体中缺失的分子。Teriparlatin [重组hPTH（1-34）]是另一种潜在的治疗方法，但它的吸引力较小，因为它是PTH的氨基末端截短形式，不会为甲状旁腺功能减退患者提供天然激素。虽然已批准用于骨质疏松症，但特立帕肽尚未开发，也未批准用于治疗甲状旁腺功能减退症。关于PTH（1-84）对该人群钙稳态的治疗作用知之甚少。关于甲状旁腺功能减退症骨骼的一般质量以及如何通过PTH（1-84）治疗改善骨骼质量的了解更少。这是一个重要的问题，因为在甲状旁腺功能减退症中，PTH缺乏与骨转换显著降低相关，这种情况可能会损害骨强度。该项目的主要目的是治疗，即确定PTH是否是甲状旁腺功能减退症的有效治疗方法。它建立在从一项小型研究中获得的数据基础上，该研究部分由FDA资助。通过进行一项双盲和安慰剂对照的研究，研究者希望清楚地证明PTH（1-84）治疗是一种安全有效的方法，可以克服单独使用钙和维生素D的管理障碍，并改善骨质量。由于这项PTH（1-84）试验的积极结果，研究者希望FDA能够审查数据，最终目标是批准PTH（1-84）作为甲状旁腺功能减退症的治疗方法。 这位研究者预计PTH（1-84）将成为这种孤儿病的治疗选择。

DESCRIPTION (provided by applicant): Hypoparathyroidism is a rare disorder in which parathyroid hormone (PTH) is markedly decreased or absent from the circulation. It is one of the few remaining hormone deficiency states for which replacement with the missing hormone has been heretofore unavailable. Without PTH, patients have abnormal calcium homeostasis characterized by hypocalcemia and high urinary calcium excretion. The current mainstay of therapy is calcium and vitamin D. This approach, however, has important clinical limitations. The large doses of calcium and vitamin D required are associated with risks of hypercalcemia, hypercalciuria and vitamin D toxicity. This approach also does not correct skeletal deficiencies due to lack of PTH. Because hypoparathyroidism is an orphan disease, investigators and funding agencies have all been reluctant to support the development of PTH as a therapy. Of the parathyroid hormone molecules that one might consider, the recent development of recombinant human PTH (1-84) is the most attractive because it is the native hormone, the very molecule that is missing in these individuals. Teriparatide [recombinant hPTH(1-34)] is another potential therapy but it is less attractive since it is an amino-terminal truncated form of PTH and would not provide the hypoparathyroid patient with native hormone. Although approved for osteoporosis, teriparatide has not been developed and is not approved for the treatment of hypoparathyroidism. Very little is known about the therapeutic effects of PTH (1-84) on calcium homeostasis in this population. Even less is known about the general quality of the skeleton in hypoparathyroidism and how it could be improved with PTH (1-84) therapy. This is an important concern, since in hypoparathyroidism, PTH deficiency is associated with markedly reduced bone turnover, a situation that can compromise bone strength. The major objective of this project is a therapeutic one, namely to determine whether PTH is an effective therapy for hypoparathyroidism. It builds upon data obtained from a smaller study funded, in part, by the FDA. By conducting a study that is now double-blinded and placebo controlled, the investigator expects to demonstrate clearly that PTH (1-84) treatment is a safe and effective way to overcome obstacles of management with calcium and vitamin D alone and to improve bone quality as well. With positive results from this trial with PTH (1-84), the investigator expects to be able to have the data reviewed by the FDA with the ultimate goal being approval of PTH (1-84) as a therapy for hypoparathyroidism. This sponsor-investigator expects PTH (1-84) to become the treatment of choice for this orphan disease.