02-01-2013, 01:45 AM
When toxins turn into medicines
Most people think that toxins can't induce anything but damage. In some sense, they are right - toxins are developed as defense mechanisms against various predators. People learned the hard way which animals and plants should be avoided. List of poisonous species is large, but luckily most of them could be easily recognized as dangerous due to specific skin coloration or weird body shape (lionfish). Morphological alert can save attacker's life if it recognizes it on time. Although people are familiar with poisonous animals for centuries, massive exploitation of the natural compounds began recently, when technological and technical discoveries provided researchers with tools needed for target isolation of toxins.
Civilized people depend on medicine. Number of available drugs is high and it continues rising; next generation of medicines is improved, as well as delivery systems used. Still, some diseases remain unbeatable and untreatable. Cancer is certainly on the top of the list. There are few major obstacles in drug discovery: it is a long-lasting and expensive process that can fail at any stage (even in the last, clinical phase). Thousands of molecules will be thrown away until one potential molecule is identified. All these reasons forced drug industry to change approach in discovery of novel drug candidates. Instead synthesizing drugs in the lab, scientists start exploring oldest and biggest known pharmacy in the world - pharmacy of nature! If you watch Donald Schulz (better known as a venom hunter), you know that everything, from platypus to fish, can be a good sources of toxins that could help scientists find potential solution for numerous diseases that are waiting to be cured. Scorpions are especially well studied and their venoms are already manufactured for treatment of various diseases:
Cancer
Scorpion venoms are efficient against numerous cancer types. Toxin isolated from Buthus martensii Karsch, known as BmK AGAP, is used against glioma (tumor of brain and spine). This neurotoxin targets sodium channels in the brain and induces apoptosis of the glioma cells. Another toxin, named chlorotoxin, isolated from the Leiurus quinquestriatus (death-stalker scorpion) could be used for the same purpose. Chemically it is a peptide that blocks small-conductance chloride channels that are found in the glioma cells. Application of cholortoxin is used in diagnostic (in the early discovery) and therapeutic purposes due to high sensitivity of chloride channels to chlorotoxin. Chlorotoxin also proved to be excellent in brain tumor imaging. When combined with fluorescent dye, it delineates tumor borders from the remaining healthy tissue and facilitates brain surgery. This toxin is safe when used in mammals but it is highly toxic for insects and it has potential to become efficient insecticide in the future. Bengalin is protein isolated from the Heterometrus bengalensis (Indian scorpion). When tested in the lab, bengaline shows potent anti-proliferative and cytotoxic effect against human leukemia cell lines. Anticancer effect was achieved through mitochondrial death cascade. BmHYA1 is a hyaluronidase isolated from the venom of Buthus martensi (Chinese red scorpion). Some breast cancers contain large amount of hyaluronan and since BmHYA1is a hyaluronidase, it successfully degrades hyaluronan and reduces the size of tumor. Excellent news regarding this toxin is that it is not associated with toxic side effects.
Epilepsy
Epilepsy is neurological disorder that affects between 30 and 40 millions of people in the world. Perfect antiepileptic doesn’t exist and those that are currently in use produce serious side effects. Toxins isolated from the Buthus martensi Karsch, named neurotoxins alpha and beta proved to be efficient in treating epilepsy in rats. BmK IT2 (beta neurotoxin) inhibits sodium channels in the hippocampus which trigger epileptic seizures.
Autoimmune diseases
Due to altered function of Kv1.3 channels in effector memory T cells, immune system recognizes its own cells as foreign bodies and destroys them. People diagnosed with autoimmune disease (like multiple sclerosis, rheumatoid arthritis…) receive immunosuppressive therapy. Kaliotoxin KTX is a neurotoxin isolated from Androctonus mauretanicus that shows great immunosuppressive properties. OSK1 is another potent toxin, derived from Orthochirus scrobiculosus that blocks Kv1.3 and prevents damaging effects of immune system.
Although close contact with scorpions can be dangerous and result in serious tissue injuries, proteins from their venoms can cure a lot of disorders when they are applied appropriately. Besides cancer, epilepsy and autoimmune disorders, scorpion venoms are used for development of drugs that treat erectile dysfunction, cardiovascular disorders, malaria or for the production of insecticides.
Most people think that toxins can't induce anything but damage. In some sense, they are right - toxins are developed as defense mechanisms against various predators. People learned the hard way which animals and plants should be avoided. List of poisonous species is large, but luckily most of them could be easily recognized as dangerous due to specific skin coloration or weird body shape (lionfish). Morphological alert can save attacker's life if it recognizes it on time. Although people are familiar with poisonous animals for centuries, massive exploitation of the natural compounds began recently, when technological and technical discoveries provided researchers with tools needed for target isolation of toxins.
Civilized people depend on medicine. Number of available drugs is high and it continues rising; next generation of medicines is improved, as well as delivery systems used. Still, some diseases remain unbeatable and untreatable. Cancer is certainly on the top of the list. There are few major obstacles in drug discovery: it is a long-lasting and expensive process that can fail at any stage (even in the last, clinical phase). Thousands of molecules will be thrown away until one potential molecule is identified. All these reasons forced drug industry to change approach in discovery of novel drug candidates. Instead synthesizing drugs in the lab, scientists start exploring oldest and biggest known pharmacy in the world - pharmacy of nature! If you watch Donald Schulz (better known as a venom hunter), you know that everything, from platypus to fish, can be a good sources of toxins that could help scientists find potential solution for numerous diseases that are waiting to be cured. Scorpions are especially well studied and their venoms are already manufactured for treatment of various diseases:
Cancer
Scorpion venoms are efficient against numerous cancer types. Toxin isolated from Buthus martensii Karsch, known as BmK AGAP, is used against glioma (tumor of brain and spine). This neurotoxin targets sodium channels in the brain and induces apoptosis of the glioma cells. Another toxin, named chlorotoxin, isolated from the Leiurus quinquestriatus (death-stalker scorpion) could be used for the same purpose. Chemically it is a peptide that blocks small-conductance chloride channels that are found in the glioma cells. Application of cholortoxin is used in diagnostic (in the early discovery) and therapeutic purposes due to high sensitivity of chloride channels to chlorotoxin. Chlorotoxin also proved to be excellent in brain tumor imaging. When combined with fluorescent dye, it delineates tumor borders from the remaining healthy tissue and facilitates brain surgery. This toxin is safe when used in mammals but it is highly toxic for insects and it has potential to become efficient insecticide in the future. Bengalin is protein isolated from the Heterometrus bengalensis (Indian scorpion). When tested in the lab, bengaline shows potent anti-proliferative and cytotoxic effect against human leukemia cell lines. Anticancer effect was achieved through mitochondrial death cascade. BmHYA1 is a hyaluronidase isolated from the venom of Buthus martensi (Chinese red scorpion). Some breast cancers contain large amount of hyaluronan and since BmHYA1is a hyaluronidase, it successfully degrades hyaluronan and reduces the size of tumor. Excellent news regarding this toxin is that it is not associated with toxic side effects.
Epilepsy
Epilepsy is neurological disorder that affects between 30 and 40 millions of people in the world. Perfect antiepileptic doesn’t exist and those that are currently in use produce serious side effects. Toxins isolated from the Buthus martensi Karsch, named neurotoxins alpha and beta proved to be efficient in treating epilepsy in rats. BmK IT2 (beta neurotoxin) inhibits sodium channels in the hippocampus which trigger epileptic seizures.
Autoimmune diseases
Due to altered function of Kv1.3 channels in effector memory T cells, immune system recognizes its own cells as foreign bodies and destroys them. People diagnosed with autoimmune disease (like multiple sclerosis, rheumatoid arthritis…) receive immunosuppressive therapy. Kaliotoxin KTX is a neurotoxin isolated from Androctonus mauretanicus that shows great immunosuppressive properties. OSK1 is another potent toxin, derived from Orthochirus scrobiculosus that blocks Kv1.3 and prevents damaging effects of immune system.
Although close contact with scorpions can be dangerous and result in serious tissue injuries, proteins from their venoms can cure a lot of disorders when they are applied appropriately. Besides cancer, epilepsy and autoimmune disorders, scorpion venoms are used for development of drugs that treat erectile dysfunction, cardiovascular disorders, malaria or for the production of insecticides.
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