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Interview with 2015 Medicine Innovation Program grant winners: Long-Acting PTH for Treatment of Patients with Hypoparathyroidism.
Hypoparathyroidism is a life-long disease that is characterized by an inadequate production of PTH and low blood calcium levels. There is currently no adequate treatment option for this disease. Dr. Michael Mannstadt and others in the Endocrine Division have developed a novel long-acting PTH analog that can elevate blood calcium levels for up to 48 hours. The Medicine Innovation Program (MIP) Grant will enable them to perform a first-in-human Phase I clinical trial of this novel compound.
Project Background: Calcium levels in the blood are vital to most organ systems and have to be kept constant day and night. There are many different mechanisms that keep calcium level constant, one of which is by a hormone called parathyroid hormone (PTH), which controls calcium levels. In addition, it controls bone health. Our research group at the Endocrine Unit, particularly Thomas Gardella, PhD, is working on the structure of PTH and how it interacts with its receptor in detail.
This research has a long tradition at Mass General: John Potts, MD has been instrumental in determining the amino acid sequence of PTH and Henry Kronenberg, MD has characterized the gene. My research group is interested in a disease that is called hypoparathyroidism, where patients do not have enough functioning parathyroid glands, commonly caused by inadvertent removal of the parathyroids during neck surgery. Patients with hypoparathyroidism have very low levels of blood calcium if untreated. Until recently it wasn’t possible to treat the disease with the missing hormone. Rather, calcium and calcitriol is typically given which does not replace the functions of PTH. We have developed a new class of PTH analogs with long duration of action. This innovation provides the opportunity to develop a drug to better treat hypoparathyroidism. Together with the RAID program at the NIH, and the DOM Innovation taskforce, we are working towards the fist-in-human use of LA-PTH.
Project Next Steps: We are working on an Investigational New Drug submission, an U.S. Food and Drug Administration requirement to allow the use of a new drug in humans. That is the part where the MIP and our group are working closely together at the moment. In addition, we are preparing the necessary Institutional Review Board documents. The goal is to launch a Phase-I trial here at MGH, where the safety of the drug is being tested. While the Phase-I trial is a relatively small trial in normal volunteers, it requires organization and input from many experts. The MIP has been helping us preparing for the Phase-I trial.
Key milestones with MIP funding: There is a well-known gap between academic researchers and the patients who need their discoveries for treatment of disease. How do you get a promising drug to humans? That is an immense and well-known challenge in biomedical research. The MIP Innovation Grant has been instrumental in helping us to cross this barrier. Together, we have worked on a business plan, on strategic planning with regards to potential partners for this project, and on working with outside experts on the IND submission.
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