Parathyroid hormone receptor activation and hematopoietic progenitor cell expansion

Patent Number: 7,429,383

Mobilization of stem cells is big money.  For example, the company Anormed was bought by Genzyme for more than half a billion dollars because of its late-phase compound, a CXCR4 antagonist which mobilizes study cells.  Why would one be interested in mobilizing stem cells out of the bone marrow?  Firstly, this is used instead of drilling holes in the bones of bone marrow donors for bone marrow transplant.  Secondly, patients with various types of cancers can have their bone marrow cells collected from peripheral circulation, purged of the malignant cells, and then after recieving high dose radiation/chemotherapy are then returned their own stem cells.  Thirdly, newer data suggests that in situations such as stroke or heart attack, bone marrow stem cells are naturally mobilized to the area of injury.  The idea would be that if one can augment this process, a type of "endogenous stem cell therapy" could be achieved.

There are many approaches and patents on ways of mobilizing bone marrow stem cells, ranging from "curious" approaches such as natural plant extracts, to toll like receptor agonists, to various cytokine cocktails.

The current patent covers enhancing growth of hematopoietic stem cells as well as mobilization of hematopoietic stem cells by the activation of the parathyroid hormone receptor using agents, amongst which are, parathyroid hormone.

Parathyroid hormone is required to control calcium levels in the body.  It activates osteoblasts to produce various factors that in turn upregulate osteoclast mediated calcium release from the bones.  In addition to its role in calcium homeostasis, several papers have demonstrated clinical evidence that parathyroid hormone mobilizes stem cells.  Additionally, animal studies have demonstrated that mobilization by parathyroid hormone can accelerate healing in the critical limb ischemia model.

View this patent on the USPTO website.