Subsequent to the success of Mozobil, a small molecule chemical antagonist of CXCR4, several companies have been working at increasing the number of available means of mobilizing patient stem cells. One recent example is TaiGen Biotechnology Co., Ltd, which announced today the presentation of Phase I and preclinical data its CXCR4 antagonist TG-0054, at the ASH Annual Meeting held in New Orleans, the US, from December 5 to 8, 2009.
Date will be presented from a randomized, double-blind, placebo-controlled, sequential ascending single intravenous dose Phase I study. According to the press release, "TG-0054 exhibited excellent and favorable safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) profile."
The study was critical because it establishes a maximally tolerated dose that can be used for efficacy-finding Phase II clinical trials. One such trial, "A Phase II, Randomized, Open-Label, Multi-Center Study to Evaluate the Safety, Pharmacokinetics, and Hematopoietic Stem Cell Mobilization of TG-0054 in Patients with Multiple Myeloma, Non-Hodgkin Lymphoma or Hodgkin Disease" will begin to enroll patients in December, 2009.
Quite interestingly, the data presented will included details of the mechanism of mobilization, as well as the surprising finding that not only were hematopoietic (blood making) stem cells mobilized into circulation, but also stem cells for the blood vessels, called "circulating endothelial progenitor cells (EPC)."
The ability of TG-0054 to cause mobilization of EPC may support its use in other areas besides hematology. For example, it is known that patients with ischemic heart disease have low circulating EPC. By increasing the number of EPC, the body may be able to grow new blood vessels around the areas of ischemia, and thus inhibit progression, or even reverse the lack of oxygen to the myocardium.
To date, the classically used stem cell mobilizer, G-CSF, has been administered in patients with heart failure for increasing blood vessel production, as well as stimulation of endogenous regenerative mechanisms. Clinical trial results have been mixed, which may be due to other underlying factors associated with cardiac degeneration. By having an arsenal of several stem cell mobilizers, each having unique properties, future studies may be able to create a treatment protocol in which the patient is given drugs that activate stem cells, and the stem cells then home to the area where the body needs them.
