Drugs currently available for the treatment of ischemic (lack of blood supply) conditions are not satisfactory. Since selectins have a primordial role in the development of ischemia, we have proposed the use of a recently discovered anti-selectin blocker (TBC-1269) in a feasibility study to determine its protective capabilities under conditions of severe liver, kidney or lower extremity ischemia in the mice.
Our specific aims -centered around commercialization of this drug- is: 1. To demonstrate its definitive therapeutic value, 2. To assess the ideal conditions of tissue and organ protection, 3. To determine if the addition of other well known drugs (eg. Verapamil-calcium channel blocker- and Nitroprusside -nitric oxide donor-) will enhance the effect of this novel anti-selectin blocker. Functional, biochemical and molecular studies -determining the response of neutrophils and CXC and C-C chemokines to the ischemic response and treatment will be utilized to characterize this drug for its use in ischemic conditions. Results of this innovative study could significantly improve the clinical means of enhancing the quality of life of million of patients suffering from the large number of maladies associated with ischemia/reperfusion injury.
There are no potent anti-ischemic drugs in the market that effectively protect the organ and life of patients suffering from ischemic diseases such as stroke, coronary artery occlusion, shock trauma, transplant related problems and others. Thus, the use of a newly discovered anti-selectin blocker in the treatment of ischemic syndromes will have a definitive effect in the commercial value of this product.
| Calvey, Colleen R; Toledo-Pereyra, Luis H (2007) Selectin inhibitors and their proposed role in ischemia and reperfusion. J Invest Surg 20:71-85 |
| Lopez-Neblina, Fernando; Toledo-Pereyra, Luis H; Toledo, Alexander H et al. (2007) Ryanodine receptor antagonism protects the ischemic liver and modulates TNF-alpha and IL-10. J Surg Res 140:121-8 |
| Lopez-Neblina, Fernando; Toledo-Pereyra, Luis H (2007) Anti-ischemic effect of selectin blocker through modulation of tumor necrosis factor-alpha and interleukin-10. J Surg Res 138:275-83 |
| Lopez-Neblina, Fernando; Toledo-Pereyra, Luis H (2006) Phosphoregulation of signal transduction pathways in ischemia and reperfusion. J Surg Res 134:292-9 |
| Lopez-Neblina, Fernando; Toledo, Alexander H; Toledo-Pereyra, Luis H (2005) Molecular biology of apoptosis in ischemia and reperfusion. J Invest Surg 18:335-50 |
| Toledo-Pereyra, Luis H; Lopez-Neblina, Fernando; Reuben, Jayne S et al. (2004) Selectin inhibition modulates Akt/MAPK signaling and chemokine expression after liver ischemia-reperfusion. J Invest Surg 17:303-13 |
