Corroles for chronic, systemic, and neurodegenerative diseases(Technion)
Current available treatment of neurodegenerative disorders (e.g. Parkinson's disease, Alzheimer's disease, Huntington disease and amyotrophic lateral sclerosis) as well as Diabetes (DM) fails to prevent disease progression (e.g. cell death / neuronal degeneration). Although these diseases ofcourse differ in their etiologies, risk factors and pathologico – clinical manifestations, they share some very basic biological mechanisms. Oxidative Stress (OS) is probably the most important of these, causing cell destruction and apoptosis. Among the free radicals causing OS, special consideration should be given to Peroxynitrite (PN), unable to be neutralized by natural defense systems at all; neither efficiently neutralized by any reagent developed so far. In addition, today's anti oxidative (AO) agents are usually not active when given orally, and lack satisfactory Blood Brain Barrier (BBB) penetration. Thus today's medications focus on specific pathological mechanisms, unique to each disease, but the global OS problem remains unsolved. Hence the conclusion that tomorrow's state of the art treatment will include today's medications together with new generation AO agents which: a. penetrate BBB, b. reduce PN, c. active when given orally, d. posses much better AO properties. According to preliminary results, these drugs may show a pioneer property of neural restoration, thus invert the natural course of degenerative diseases.Metallocorroles (MC) are metallo-porphyrin based decomposition catalysts of PN, possess very potent AO activity, and their structural and electronical variables can be easily manipulated. The latter should be noticed since besides having superior AO properties per se, it also holds a favorable possibility to succeed in fields where the hitherto developed AO agents have failed (e.g. bio – distribution). The latter is possible thanks to recent advancements in the field of corroles' synthesis. In addition, preliminary results point that MC also act in cell cyto-protection via signaling pathways, which probably endows them with even greater effect in vivo. This also should be studied.
Applications of MC in medical field are for conditions as discussed above, given combined or monotherapy, as protective therapy in other medical conditions, as AO agents in cosmetical products, and any other drugs that might benefit from AO properties. One should note that the research that will be done in developing these drugs may accompany with patents in the fields of chemistry, drug productions, etc.
Some Market Estimation:
Prevalence of Diabetes worldwide: 171,000,000 (yr. 2000) -> 366,000,000 (yr .2030) [WHO]
Prev. of Alzheimer in USA: 9 milion (yr. 2000, 65y/o and older) -> 15.5 million (yr. 2030) [NIH]
DRS-1019
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