Use of BDNF to Treat Microvascular Disease
- *Abstract
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As their name suggestions, neurotrophins are typically considered to be involved in the survival and function of neurons. Investigators at the Weill Cornell Medical College and at Harvard made the surprising finding that neurotrophins play critical roles in vascular formation and growth, and are required for the stabilization of cardiac vessels and other microvascular beds through direct trophic actions on endothelial cells.
Although preclinical and clinical trials of VEGF and other growth factors to promote angiogenesis are ongoing, VEGF faces significant challenges with toxicity and efficacy -- vessels formed under the stimulus of VEGF tend to be unstable and leaky. Very little has been known about growth factors that regulate stabilization and survival of the mature vasculature. It now appears that while VEGF jump-starts the angiogenic process, BDNF is required to stabilize newly formed vessels and to maintain them in their maturity.
The Weill Cornell lab has produced new vessels in mice using BDNF delivered via gene therapy and in protein form. Work in pigs is forthcoming. As BDNF has been administered to humans in clinical trials for ALS, in which BDNF showed no efficacy but also little toxicity, human trials can follow if the preclinical work remains promising.
Potential Applications
Treatments for chronic wounds, cardiac ischemia, congestive heart failure, and other tissue ischemia secondary to vascular insufficiency.
- *Licensing
- Brian J. Kellybjk44@cornell.edu212-746-6186
- 其他
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- Shmelkov SV et al. (2005) Cytokine preconditioning promotes codifferentiation of human fetal liver CD133+ stem cells into angiomyogenic tissue. Circulation 111(9):1175-83.
- 国家/地区
- 美国
