Novel Treatment for Angiogenesis-dependent Diseases
Inventors: Donald Ingber, Abigail Bracha, Kaustabh Ghosh, Akiko Mammoto, Arvind Ravi, Benjamin Matthews, Charles Thodeti
Invention Types: Therapeutics
Research Areas: Oncology/Hematology, Ophthalmology
Keywords: Anti-angiogenesis, Ion ChannelsFor More Information Contact: Dietz, Ryan
The vascular endothelial growth factor (VEGF) family of growth factors controls pathological angiogenesis in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In addition to VEGF, other microenvironmental signals, such as mechanical forces conveyed by the extracellular matrix, control blood vessel formation. Drs. Ingber and Mammoto have identified a new mechanosensitive signaling pathway that modulates angiogenesis. They have shown, using siRNA and overexpression studies in human microvascular endothelial cells in vitro and in an in vivo neonatal mouse retina assay, that p190RhoGAP controls VEGF receptor 2 expression by altering the balance of two antagonistic transcription factors, TFII-I and GATA2.
The discovery by Drs. Ingber and Thodeti indicate that TRPV4 may be a novel target for therapies of angiogenesis-dependent diseases, such as cancer, arthritis and macular degeneration. TRPV4 inhibitors would inhibit angiogenesis, whereas activators might increase capillary growth.
Any of the angiogenesis-dependent diseases represent unmet medical needs. Members of the TRP ion channel family and TRPV4 in particular are actively being pursued as drug targets, especially for pain and inflammation indications. The work by Drs. Ingber and Thodeti suggest pursuing TRPV4 as targets for angiogenesis modulation, both alone and in combination in the future.
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Key Publications: Circulation Research 2009 April 9 [epub ahead of print]
IPStatus: Pat. Pend.