Velcade guides stem cells to bone
Boston, Massachusetts -
Stem cell therapeutics are difficult to commercialize because of the need for cellular manipulation. Even business models that involve off the shelf universal stem cells have the issue that you need are selling an actual biologic product, a product that is very difficult to standardize and ensure quality control
A much more attractive method of commercializing stem cell therapeutics involves the use of small molecule drugs that can activate endogenous stem cells. This approach is ideal since the infrastructure and regulatory pathways for small molecule drugs are much more defined than for biologics. The interest in small molecule drugs that modify stem cell activity can be seen by the recent founding of the company Fate Therapeutics, even though the company did not even have candidates when they raised money.
Even more attractive than developing small molecule agents that target stem cells is the ability of finding drugs already in clinical use that can target stem cell activities. This way you don't need to do any development, with exception of some proof of concept efficacy studies. This is exactly what was done in a recent paper from Harvard Mukherjee et al. Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest. 2008 Jan 24
The investigators used the clinically approved drug velcade (also called bortezomib or PS-341, made by Millenium Pharmaceuticals) an inhibitor of NF-kB, which acts by inhibiting proteosomes, to induce mesenchymal stem cell differentiation into bone cells.
Specifically, they demonstrated that treatment with velcade targets the Runx-2 DNA-binding protein which is involved in osteogenesis.
The researchers demonstrated that administration of mesenchymal stem cells to mice recieving velcade results in the mice developing ectopic bone (note to self, if your on velacade don't take MSCs !!).
More physiologically relevant, velcade was able to ameliorate pathology in a murine model of osteoporosis.
This is surely to be one of many to come in terms of using already approved pharmaceuticals to modify stem cells. Other examples of this include the use of valproic acid to activate endogenous stem cells, as well as the administration of the pregnancy associated compound human chorionic gonadotropin to stimulate hematopoiesis, or erythropoietin to stimulate neurogenesis.
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2 Comments | Add Comment
Paula Gobba said...
Velcade has helped my uncle go into remission. I think that revlemid also has great activity against myeloma. But this is new to me that it actually can help bones.
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Tania Watts said...
I find it very interesting and almost to the point of disbelieve that Velcade induces osteogenesis. If this was the case then why have clinicians administering this agent not seen an increase in bone density?
In general clinicians are the first to make these observations, this is especially true in the situations where the drug is used to treat a condition that actually messes up the bones !!
Yes, myeloma is a bone disease. Well bone marrow. So I really wonder if the data presented in this JCI paper really is real or is just some PhD trying to make a name himself by making a story up in mice.