Scorpion Venom

Leiurus quinquestriatus which means death stalker scorpion is a cunning killer that lives in the desert in places like the Middle East and Northern Africa. Hiding under natural burrows and stones this deadly scorpion waits patiently for its victims to pass by before striking an attack. The scorpion's venom is packed with lethal enzymes, enzyme inhibitors, histamines and neurotoxins that enter the victim's brain to attack nervous tissue. One of the key players is called chlorotoxin. From earthworms, crickets and even humans the immediate stroke of its tail delivers a poisonous punch.

The scorpion's sting releases a venomous cocktail that can lead to cardiac and respiratory complications and death in humans, especially children. Ironically, researchers believe the dangerous death stalker scorpion's venom also holds the key to saving lives. Many studies have shown that by itself chlorotoxin does not cause harmful effects in mice or humans. So the story of the death stalker scorpion unfolds slowly from villainous killer to kingly victor with the discovery of its chlorotoxin.

Brain Cancer Challenges

The use of chlorotoxins as a treatment for brain cancer started out as a question posed over 20 years ago by Dr. James Olson of the Fred Hutchinson Cancer Research Center. He asked, "Wouldn't it be interesting if we could light up a cancer cell?"

The question was not only raised by Dr. Olson - scientists and brain surgeons also hypothesized over a way to distinguish normal brain tissue from cancerous tissue. A continuing challenge for surgeons who normally rely on color, texture, blood supply and their expertise to find tumors - not really a precise approach.

Gliomas are a common form of brain cancer that leaves patients with extremely bad headaches, nausea, seizures and cranial nerve disorders. Most patients that are diagnosed with gliomas live an average of one year and very few live beyond three years. Approximately 20,000 people will be diagnosed with a malignant brain or spinal cord tumor this year alone. And close to 65% of those children and adults are expected to die.

The issue lies with the lack of available technology to make the tumor and normal brain tissue easily distinguishable. Currently, the approach to remove brain cancer makes it very difficult to treat patients. The dilemma of cutting out too little means the tumor will most likely come back and if the surgeon removes too much it may result in irreversible brain damage.

Research Lights up Tumors

The answer to isolating tumors for surgical removal appears to be chlorotoxin. That's why today Dr. Olson with the help of Dr. Richard Ellenbogen, Dr. Patrick Gabikian and others are able to study the properties of chlorotoxin through privately funded research.

With about 80% of malignant cancers showing up along the same edges of the surgical cut, chlorotoxin could hold an important key to helping surgeons paint tumors. Painting the tumor sections will help brain surgeons easily tell the difference between cancer tissue and normal brain tissue.

Here are some important findings:

1. Dr. Gabikian found literature citing the effects of chlorotoxin on cancer cells.
2. Research demonstrated that the chlorotoxin was able to bind to glioma cells.
3. Dr. Olson began looking for ways to light up chlorotoxin so that when bound to cancer cells it would make them visible.
4. Olson's research group found that chlorotoxin binds well with the fluorescent compound, Cy5.5 which was developed by Invitrogen.
5. Dr. Gabikian injected a small amount of the coupled compound, Chorotoxin:Cy5.5 into the bloodstream of test mice with human glioma.
6. Images of the test mice revealed tumors in the brains that lit up while normal tissue remained untouched by chlorotoxin.
7. The term tumor paint was coined when further studies where conducted in mice with other cancers (i.e. prostate cancer) and those cancer cells lit up as well.

MRIs are one of the imaging detection methods used to make a distinction between normal tissue and cancer tissue. The hitch is that there must be more than 1 million cancer cells for the MRI to detect a tumor. Compare that to tumor paint which can pick up as few as 200 cancer cells.

The Future of Tumor Paint

In less than two years, Olson would like to see tumor paint as the newest addition of surgical arsenal used to fight brain cancer. Before that day comes Chlorotoxin:Cy5.5 must first go through a battery of tests and toxicity studies before beginning clinical trials. And while chlorotoxin on its own is not harmful to humans, the FDA does not feel the same about the dye being used with it. Consequently, the fluorescent dye has not been approved by the FDA. The potential for Leiurus quinquestriatus' chlorotoxin to identify brain tumors is promising. With hurdles to overcome, Olson is prepared to continue his research despite criticism and speculation.

Olson says, "When this idea was proposed to the National Cancer Institute, it was perceived as highly speculative and ambitious...I think it is a beautiful gift, not only to those who have brain cancer, but as a prospective test for all cancer, if this bears fruit."

And if his labor proves to be fruitful what a beautiful gift to patients it will be.

Source: http://www.fhcrc.org/about/pubs/quest/win07/scorpion.html