New York University College of Dentistry's (NYU Dentistry) Nicola Partridge, PhD, has been awarded a five-year, $1.9 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to investigate potential new compounds for the treatment of osteoporosis.
The federally funded grant will support bench research aimed at understanding how the protein hormone, parathyroid hormone-a related protein-and a drug analog that mimics the protein called abaloparatide, interact in the surface of a cell in bone and affect bone formation and breakdown.
All three of these hormones are currently being investigated for the treatment of osteoporosis and the latter two are believed to have a wider therapeutic window than teriparatide (short form of parathyroid hormone) injection, commonly used for severe osteoporosis.
"With this grant, we hope to understand the molecular mechanisms, pathways, and interactions at the cellular level that affect bone building and breakdown," said Dr. Partridge. "Learning how these hormones, related proteins, and its analog work will help us develop new treatments that are better tolerated for osteoporosis," said the professor and chair of NYU Dentistry's Department of Basic Science and Craniofacial Biology, and an authority on molecular endocrinology and bone and mineral research.
Dr. Partridge and her team know that parathyroid hormone is essential for maintaining serum calcium levels. The bench research will investigate specifically how parathyroid hormone functions at the cellular level, compared with the related protein, and the drug analog abaloparatide.
In particular, the investigators hope to learn whether the protein and drug analog might provide a better treatment than parathyroid hormone for osteoporosis or teriparatide, as well as other bone and skeletal deteriorative disorders. Previous research suggests that the two latter drugs are superior to teriparatide, resulting in lower bone resorption. Abaloparatide has been shown to yield a greater increase in bone mineral density, especially in the hip.
"Osteoporosis exacts a heavy disease burden at the societal and individual levels," said Dr. Partridge. "Ours is the only research group in the world that has determined the transcriptional action of parathyroid hormone. We characterized co-activator and co-repressor proteins interacting with bone-specific transcription factors in response to this hormone. We are well positioned to further investigate how these molecules work at the cellular level, thereby providing support for a new osteoporosis drug."
According to the National Institutes of Health, there are approximately 1.5 million osteoporotic fractures in the United States each year that lead to half a million hospitalizations, over 800,000 emergency room encounters, more than 2,600,000 physician office visits, and the placement of nearly 180,000 individuals in nursing homes. Hip fractures are by far the most devastating type of fracture, accounting for about 300,000 hospitalizations each year. At the individual level, a fractured hip can lead to a downward spiral in quality of life, mobility, and physical and mental health. Within a year after a hip fracture, individuals are at increased risk for death. About one in five people sustaining a hip fracture ends up in a nursing home.
Acknowledgements: NIH/National Institute of Diabetes and Digestive Kidney Diseases 2R01DK047420
About New York University College of Dentistry: New York University College of Dentistry (NYU Dentistry), is the third oldest and the largest dental school in the US, educating more than 8 percent of all dentists. NYU Dentistry has a significant global reach and provides a level of national and international diversity among its students that is unmatched by any other dental school. http://www.