Deathstalker Scorpion Venom

Could Improve Gene Therapy

for Brain Cancer

Science (Aug. 11, 2010) — An ingredient in the venom of the “deathstalker” scorpion could help gene therapy become an effective treatment for brain cancer, scientists are reporting. The substance allows therapeutic genes — genes that treat disease — to reach more brain cancer cells than current approaches, according to the study in ACS Nano.

Miqin Zhang and colleagues note that gene therapy — the delivery of therapeutic genes into diseased cells — shows promise for fighting glioma, the most common and most serious form of brain cancer. But difficulties in getting genes to enter cancer cells and concerns over the safety and potential side effects of substances used to transport these genes have kept the approach from helping patients.

The scientists describe a new approach that could solve these problems. Key ingredients of their gene-delivery system are chlorotoxin, the substance in deathstalker scorpion venom that can slow the spread of brain cancer, and nanoparticles of iron oxide. Each nanoparticle is about 1/50,000th the width of a human hair. In tests on lab mice, the scientists demonstrated that their venom-based nanoparticles can induce nearly twice the amount of gene expression in brain cancer cells as nanoparticles that do not contain the venom ingredient. “These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers,” the article notes.

Sourced & published by Henry Sapiecha

Green Tea Extract

Appears to Keep Cancer in Check

in Majority of CLL Patients

Science (June 4, 2010) — An extract of green tea appears to have clinical activity with low toxicity in chronic lymphocytic leukemia (CLL) patients who used it in a phase II clinical trial, say researchers at Mayo Clinic.

The findings were presented June 7 during the annual meeting of the American Society of Clinical Oncology (ASCO). They are the latest in a series of Mayo studies to show promise for use of the chemical epigallocatechin gallate (EGCG) — the major component of green tea — in reducing the number of leukemia cells in patients with CLL. Mayo first tested EGCG in a variety of laboratory assays about eight years ago, and it was found to reduce the survival of CLL leukemic cells. This laboratory finding was followed by a successful phase I clinical trial — the first time green tea extract had been studied in CLL patients.

“Although only a comparative phase III trial can determine whether EGCG can delay progression of CLL, the benefits we have seen in most CLL patients who use the chemical suggest that it has modest clinical activity and may be useful for stabilizing this form of leukemia, potentially slowing it down,” says Tait Shanafelt, M.D., a Mayo Clinic hematologist and lead author of the study.

“These studies advance the notion that a nutraceutical like EGCG can and should be studied as cancer preventives,” says Neil Kay, M.D., a hematology researcher whose laboratory first tested the green tea extract in leukemic blood cells from CLL patients. “Using nontoxic chemicals to push back cancer growth to delay the need for toxic therapies is a worthy goal in oncology research — particularly for forms of cancer initially managed by observation such as CLL.”

Drs. Shanafelt and Kay caution that EGCG is not a substitute for chemotherapy. All of the patients Mayo tested with EGCG were early stage, asymptomatic CLL patients who would not otherwise be treated until their disease progressed. The extract was supplied by the National Cancer Institute (NCI) and Polyphenon E International for these initial clinical trials.

CLL is a blood cancer that is a hybrid between leukemia and lymphoma. Progression of the disease is measured by the quantity of leukemia cells in the blood and bone marrow as well as enlargement of lymph nodes due to infiltration by the leukemia cells. In the phase I study, published in May 2009 in the Journal of Clinical Oncology, researchers found that the blood lymphocyte (leukemia cell) count was reduced in one-third of participants, and that the majority of patients who entered the study with enlarged lymph nodes due to involvement by CLL saw a 50 percent or greater reduction in their lymph node size.

Using the highest dose tested in the phase I study, the researchers launched their phase II clinical trial in an additional 36 patients. The results presented at the ASCO meeting evaluate the effects in these 36 patients as well as the six patients from the phase I trial treated at the same dose (total 42 patients). Results from 41 patients who have completed the study show that 31 percent of patients had a 20 percent or greater sustained reduction in blood leukemia count, and 69 percent of patients with enlarged lymph nodes saw a reduction of node size of 50 percent or greater.

In all, 69 percent of CLL patients had a biological response to EGCG as evidenced by a 20 percent or greater sustained reduction in blood lymphocyte count and/or a 50 percent or greater reduction in lymph node size, the researchers say.

Because EGCG was being studied in patients who did not otherwise need treatment, the researchers took a rigorous approach toward studying side effects. Most clinical trials of therapeutic agents only report grade 3 and higher side effects, but the researchers looked at and reported grade 1 and grade 2 as well. While a number of patients had transient grade 1 or 2 side effects, only three of 42 experienced a grade 3 side effect during their six months of treatment.

“All in all, the treatment was well tolerated with very mild side effects in most patients,” Dr. Shanafelt says.

The researchers say that the prior publications on the effects of EGCG on CLL leukemia cells in the laboratory and the data from the published phase I study have been widely disseminated via the Internet by patient advocacy groups. Based on information from patients and colleagues throughout the country, the Mayo researchers have become aware that many CLL patients nationwide have started to use EGCG supplements, which are readily available over the counter.

“Without a phase III clinical trial, we cannot make a recommendation that EGCG be used by CLL patients, but those who want to take supplements should consult with their oncologists and need to receive appropriate monitoring using laboratory tests,” Dr. Kay says.

The study was funded by grants from the NCI, the Mayo Comprehensive Cancer Center and from donors and patient advocacy foundations.

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3D imaging technique provides clearer roadmap to remove deadliest form of skin cancer

Even though melanoma is one of the less common types of skin cancer, it accounts for the majority of skin cancer deaths – around 75 percent. The five-year survival rate for early stage melanoma is very high (98 percent), but the rate drops precipitously if the cancer is detected late or there is recurrence. So a great deal rides on the accuracy of the initial surgery, where the goal is to remove as little tissue as possible while obtaining “clean margins” all around the tumor. So far no imaging technique has been up to the task of defining the melanoma’s boundaries accurately enough to guide surgery – until now. Read More

Received & published by Henry Sapiecha

STD linked to skin cancer

Well, well, well – it looks like the mainstream has accidentally stumbled upon the truth that skin cancer might be caused by something other than the sun. Researchers have found that some strains of HPV, a common sexually acquired virus, can dramatically increase your skin cancer risk.
Read the full story.

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Gumbi Gumbi & the cancer sure claim

Gumbi Gumbi: Rare member of family Pittosporaceae

Gumbi Gumbi is a medium to large tree, native to certain areas of Australia only, and very sparsely found. Because of its scarcity, but similarity in appearance to other species, it is often confused with trees more widely found.

Many people believe there to be as many as six varieties with only one having medicinal properties and another being toxic. Our investigations and experimentation with propagation suggests this is not the case at all. We believe there is only one true Gumbi Gumbi.

Currently Gumbi Gumbi is extremely rare, as only one tree is found growing naturally in an average of 400 sq/km (250 sq/miles) and it is not being farmed to any large extent. One significant reason for its rarity is that Gumbi Gumbi saplings and young trees are commonly ravaged by wildlife and roaming farm stock, such as Kangaroos and cattle, prior to reaching maturity. Animals instinctively know what is good for them, as did the early indigenous people. We modern people, on the other hand, are only now beginning to understand.

Gumbi Gumbi trees are by nature very slow growing and difficult to propagate. In order to ensure the required properties are inherent within trees grown in other than their naturally occurring environment; certain conditions have to be met. Mature trees develop a taproot to 60 feet in natural conditions. Many people have attempted to grow Gumbi Gumbi from seeds and saplings and failed to attain mature trees.

Scientific Analysis

Tests undertaken using Leaf and Leaf Extract from Gumbi Gumbi Natural plantation (Central Queensland, Australia)

Summary
Gumbi Gumbi contains significant amounts of elements known to aid in benefiting health.

Further testing has also shown Gumbi Gumbi to be very high in Saponins. This assists with the delivery of the inherent benefits of Gumbi Gumbi Leaf when used as a tea as per our brewing instructions.
TEST REPORT — Chemical Analysis
Gumbi Leaf: 5 July 2006

TEST REPORT — Chemical Analysis
Gumbi Tea: 21 September 2006

Note:
Concentrations in ppm are equivalent to mg/Kg or mg/L
N.D. = Not Detected

Constituent Summary of extracts of Pittosporum Angustifolium (gumbi gumbi)

Saponins:

The major constituent of gumbi gumbi extract was found to be saponin (a sulphonated di- or tri- terpene). Saponins are natural detergents found in plants (that is, they contain water soluble and fat soluble components and dissolve in water to form a stable soapy froth).

Saponins have commercial uses in a number of applications such as in beverages such as root beer and slurpies (to provide the foamy “head”). Saponins have also found application as emulsifiers for photographic film preparations and cosmetics (such as shampoos and lipsticks) and as industrial frothers for ore separation. Saponins also have anti bacterial and anti-fungal properties1. Saponins decrease blood lipids, lower blood glucose response, and as an antidote to acute lead poisoning2.

Extracts containing saponins currently have a wide application. For example, they are used in animal livestock production facilities for ammonia and odour control as well as in gut bacteria control. Certain saponins form strong insoluble complexes with cholesterol which has application in cholesterol lowering in humans. Bile acids metabolised by bacteria in the colon form secondary bile acids, some of which are known promoters of colon cancer. The feeding of saponins to laboratory mice has shown a reduction in the formation of preneoplastic colon lesions1. This has a potential in the prevention and treatment of colon cancer in humans. Saponins also have application as use for adjuvants in vaccines (adjuvants increase immune-stimulation, by using saponins their emulsifying properties can also be utilised).

Saponins are highly toxic to cold blooded animals and some have been identified in snake venom, starfish, and sea cucumber. Some are toxic to humans.

Tannins:

The term tannins is widely applied to large polyphenolic compounds that contains sufficient hydroxyl and/or carboxyl groups to form complexes with proteins and other large molecules. Tannins are classified into two groups — notable hydrolysable tannins, and condensed tannins. The term tannin refers to the use of tannins in tanning animals hides.

Tannins are almost ubiquitous in the plant kingdom. They are astringent and bitter in taste. Their astringency causes the dry and puckery feeling in the mouth following consumption of red wine, strong tea or un-ripened fruit.

They are also predominantly responsible for the colour of the above and hydrolysable tannins have long-term antioxidant properties (the reaction of hydrolysable tannins in red wine is attributable to the “maturing” of the wine). Tannins are found in fruits, berries, smoked foods, beer and wines (more tannin is found in red wines than in white), citrus juices, condiments (such a cloves, tarragon, vanilla and cinnamon), legumes, and chocolate3. Tannins have shown potential antiviral, antibacterial, and anti parasitic properties. They have also been studied for their effects on the treatment of cancers and their inhibitory effect on HIV.

Alkaloids:

Alkaloids are naturally occurring chemical compounds containing basic nitrogen functionality.

There are three main types of alkaloids — true alkaloids, proto alkaloids, and pseudo alkaloids. Both true alkaloids and proto alkaloids are derived from amino acids, while pseudo alkaloids are not derived from amino acids.

Alkaloids are alkaline and they are reactive compounds that have pharmacological effects at low doses and are used as medications and recreational drugs. Cocaine, caffeine, nicotine, and Quinine are all examples of alkaloids. Alkaloids form water soluble salts and may exist in the free-state, as salts, or as N-oxides — depending on pH or physiological conditions. These properties make them have enormous application as medications.

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Snake Venom Studies Yield Insights

for Development of Therapies

for Heart Disease and Cancer

Science(July 30, 2010) — Researchers seeking to learn more about stroke by studying how the body responds to toxins in snake venom are releasing new findings that they hope will aid in the development of therapies for heart disease and, surprisingly, cancer.

The Japanese team is reporting in a Journal of Biological Chemistry “Paper of the Week” that they are optimistic that inhibiting a protein found on the surface of blood cells known as platelets may combat both irregular blood clotting and the spread of certain cancers throughout the body.

“The finding that platelets not only play a role in blood clotting but also in the development of vessels that allow tumors to flourish was quite unexpected and paves the way for new research on the role or roles of platelets,” says Katsue Suzuki-Inoue, the associate professor at the University of Yamanashi who oversaw the 13-person team’s work in professor Yukio Ozaki’s laboratory.

About platelets, blood clots and stroke

Under normal conditions, platelets are activated to become sticky when blood vessels are injured, and their clumping together (aggregation or clotting) naturally stops bleeding. But, irregular platelet aggregation caused by disease can lead to dangerous clots or even stroke if a clot clogs or bursts in a vessel that carries oxygen and nutrients to the brain.

“When a blood clot, or thrombus, forms during the body’s normal repair process, it’s doing its job,” says Suzuki-Inoue. “But, thrombotic diseases, such as heart attack and stroke, are leading causes of death in developed countries. Understanding and manipulating the underlying chemical reactions could help us save many lives.”

But what does this have to do with snake venom? It’s sort of a long story.

How venom can prevent or cause clotting

“Snake venom contains a vast number of toxins that target proteins in platelets,” says Yonchol Shin, an associate professor at Kogakuin University who specializes in snake toxins. “Some of those toxins prevent platelets from clotting, which can lead to profuse bleeding in snake bite victims. Others, like the one we’ve focused this research on, potently activate platelets, which results in blood clots. Identification of the molecular targets of many of these toxins has made an enormous contribution to our understanding of platelet activation and related diseases.”

Intrigued by the then-recent discovery that elements in snake venom can promote irregular aggregation of platelets — the kind that leads to clots and stroke — Inoue’s and Ozaki’s team set out in 1997 to understand better the molecular underpinnings of those chemical reactions. They hoped that whatever they learned could be applied to the search for new therapies for irregular blood clotting caused by disease.

In 2000, another set of investigators came across a protein on the surface of platelets and dubbed it C-type lectin-like receptor 2, or CLEC-2. At the time, it remained unclear how CLEC-2 was produced or what its job was, but the team suspected it was worth further study.

After six years of research and collaborations with British investigators, the team in 2006 discovered how rhodocytin — a molecule purified from the venom of the Southeast Asia pit viper Calloselasma rhodastoma — binds to the CLEC-2 receptor protein on the platelet surface, spurring the platelet to clot with others like it.

Then, in another JBC “Paper of the Week” in 2007, Suzuki-Inoue and her colleagues reported how a separate molecule, called podoplanin, binds to the CLEC-2 platelet receptor protein very much like the venom molecule does. Discovered in 1990, podoplanin is a protein expressed on the surface of cancer cells, and, when bound to the CLEC-2 receptor on platelets, it spurs blood clotting, too.

“To shield themselves from the immune system, cancer cells send out a chemical, podoplanin, which binds to the CLEC-2 receptor protein on platelets, telling the platelets to get together and form a protective barrier around the cancer cells. Once enveloped, the cancer cells are not detected by the immune system and are able to bind to blood vessels’ inner linings and spread, or metastasize, throughout the body,” she explained.

Using a mouse model, the team in 2008 showed that blocking the tumor protein podoplanin from binding with the platelet receptor protein CLEC-2 could prevent tumors from metastasizing to the lung.

From snake venom to platelets to tumors

The recent investigations by the team, published in the JBC online July 4, hinged on the generation and study of genetically engineered mouse embryos that lacked the platelet receptor protein CLEC-2. In the end, the experiments showed that CLEC-2 is not only necessary for blood clotting but also necessary for the development of a different type of vessel, specifically lymphatic vessels that carry fluid away from tissues and prevent swelling, or edema.

“During fetal development, the CLEC-2 deficiency disturbed the normal process of blood clotting and, in fact, the normal development and differentiation of blood and lymphatic vessels,” says Masanori Hirashima, an associate professor at Kobe University. “They had disorganized and blood-filled lymphatic vessels and severe swelling.”

Podoplanin, Hirashima explains, is also expressed on the surface of certain types of lymphatic cells and is known to play a role in the development of lymphatic vessels: “These findings suggest that the interaction between CLEC-2 and podoplanin in lymphatic vessels is necessary for the separation between blood vessels and lymphatic vessels.”

It has been known that tumors generate blood vessels to promote their growth, and it’s possible that the formation of lymphatic vessels also may contribute to the spread of cancer throughout the body, says Osamu Inoue, an assistant professor at the University of Yamanashi.

“We speculate that the interaction between the platelet’s CLEC-2 protein and the podoplanin molecule in lymphatic cells plays an essential role in the creation of lymphatic vessels, thereby facilitating tumor growth. If this is the case, a drug that blocks that interaction would prevent the spread of tumors through lymphatic vessels,” Inoue said.

By being deemed a “Paper of the Week,” the team’s work is categorized in the top 1 percent of papers reviewed by the JBC editorial board in terms of significance and overall importance. Other contributors included Guo Ding, Satoshi Nishimura, Kazuya Hokamura, Koji Eto, Hirokazu Kashiwagi, Yoshiaki Tomiyama, Yutaka Yatomi and Kazuo Umemura.

Sourced & published by Henry Sapiecha

Saving Eyes

Ocular Oncologists Inject Drug Into Eye

To Starve Tumors And Save Sight

October 1, 2008 — Ocular oncologists adopted a drug originally intended to treat colon cancer as a treatment for cancers in the eye as well as macular degeneration. The drug reduces abnormal blood vessel growth, which starves tumors and stops blood vessels from leaking. This interrupts the processes that would, if not stopped, greatly damage patients’ vision.

Whether it’s cancer or macular degeneration, many times patients must face the reality that they will go blind. Now, a new treatment is helping save their sight.

The first thing everyone notices about Dove Karn is her beautiful blue eyes — and it was in Central Park where she came to terms with the fact that she had melanoma in one of those very eyes.

Her tumor was treated with radiation — but the side effects could destroy her vision. Ocular oncologist Paul Finger turned to a new drug to stop Dove’s vision from slipping away.

“It’s a real paradigm shift — like antibiotics were for infections,” says Paul Finger, M.D., an ocular oncologist at the New York Eye Cancer Center in New York City. “This anti-blood-vessel drug is saving people’s vision.”

Avastin is a shot given directly into the eye. It starves the tumor by stopping the growth of abnormal blood vessels that normally would feed the tumor.

“Avastin stops new blood vessels from growing, but it also prevents new and old blood vessels from leaking — and the leaking is what takes away most of the patient’s vision,” Dr. Finger said.

Dove will need to get shots every 6 to 8 weeks, indefinitely — but she says it’s worth it.

“This year was the year that I could say I’m in remission,” Karn said. “I have a full-time teaching job. My children are fabulous — life is wonderful right now.”

ABOUT CANCER IN THE EYE: Ocular melanoma — eye cancer — is a particularly rare and aggressive form of cancer that attacks the pigment cells in the retina. There are essentially two types of intraocular melanoma: low-grade tumors, which grow slowly and rarely metastasize, and high-grade tumors, which grow more quickly and metastasize at a very early stage. Once a tumor metastasizes, the cancer spreads quickly to the liver and other organs, and a patient has only 6 to 12 months to live in the worst cases, although some can survive for as long as 5 years. The National Eye Institute estimates some 2,000 newly diagnosed cases of ocular melanoma occur per year in the United States and Canada –roughly seven in one million people. It affects people of all ages and races, and is not hereditary. Ocular melanoma kills nearly half of those who develop it.

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Morphine Blocks Tumor Growth,

Study Suggests

Science (July 28, 2010) — Current research suggests that taking morphine can block new blood vessel and tumor growth. The related report by Koodie et al, “Morphine suppresses tumor angiogenesis through a HIF1?/p38MAPK pathway,” appears in the August 2010 issue of the American Journal of Pathology.

Morphine is currently the gold standard of analgesics used to relieve severe pain and suffering. Angiogenesis, or new blood vessel growth, is critical for tumor progression from dormant to malignant. Morphine is commonly used to treat cancer pain, but the effects of morphine use on new blood vessel and tumor growth remain controversial.

Using a clinically relevant morphine dose in a mouse model of Lewis lung carcinoma, researchers led by Dr. Sabita Roy of the University of Minnesota Medical School in Minneapolis, MN examined the effect of morphine use on new blood vessel growth in tumors. They found that chronic morphine use decreased levels of tumor angiogenesis in a manner dependent on the opioid receptor. This effect was mediated by suppression of signaling induced by low oxygen concentrations, leading to a reduction in the levels of pro-angiogenic factors. Therefore, morphine may not only serve as an analgesic for cancer patients, but may also inhibit tumor angiogenesis and growth.

Koodie et al conclude that “morphine is a potential inhibitor of tumor growth, through the suppression of tumor cell-induced angiogenesis and hypoxia-induced p38 MAPK activation of HIF-1. In addition to its analgesic potential, morphine can be exploited for its anti-angiogenic potential in cancer pain management; these findings support the use of morphine for cancer pain management.”

This work was supported by the National Institutes of Health

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Do Cleaning Products & Sprays

Cause Breast Cancer?

Science (July 21, 2010) — Women who report greater use of cleaning products may be at higher breast cancer risk than those who say they use them sparingly. Researchers writing in BioMed Central’s open access journal Environmental Health asked more than 1500 women about their cleaning product usage and found that women who reported using more air fresheners and products for mold and mildew control had a higher incidence of breast cancer.

Julia Brody, from the Silent Spring Institute, USA, worked with a team of researchers to carry out telephone interviews with 787 women diagnosed with breast cancer and 721 comparison women. She said, “Women who reported the highest combined cleaning product use had a doubled risk of breast cancer compared to those with the lowest reported use. Use of air fresheners and products for mold and mildew control were associated with increased risk. To our knowledge, this is the first published report on cleaning product use and risk of breast cancer.”

The researchers questioned women on product use, beliefs about breast cancer causes, and established and suspected risk factors. They found that cleaning products, air fresheners, and insect repellents were associated with breast cancer, but little association was observed with overall pesticide use. Women with breast cancer who believed that chemicals and pollutants contribute ‘a lot’ to the risk of developing the condition were more likely to report high product usage.

Speaking about this potential bias to the study, Brody said, “When women are diagnosed with breast cancer, they often think about what happened in the past that might have contributed to the disease. As a result, it may be that women with breast cancer more accurately recall their past product use or even over-estimate it. Or, it could also be that experience with breast cancer influences beliefs about its causes. For example, women diagnosed with breast cancer are less likely to believe heredity contributes ‘a lot’, because most are the first in their family to get the disease.”

In order to avoid possible recall bias, the researchers recommend further study of cleaning products and breast cancer using prospective self-reports and measurements in environmental and biological media.

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Of Bugs and Brains:

Gut Bacteria Affect Multiple Sclerosis

Science (July 20, 2010) — Biologists at the California Institute of Technology (Caltech) have demonstrated a connection between multiple sclerosis (MS) — an autoimmune disorder that affects the brain and spinal cord — and gut bacteria.

The work — led by Sarkis K. Mazmanian, an assistant professor of biology at Caltech, and postdoctoral scholar Yun Kyung Lee — appears online the week of July 19-23 in the Proceedings of the National Academy of Sciences.

Multiple sclerosis results from the progressive deterioration of the protective fatty myelin sheath surrounding nerve cells. The loss of myelin hinders nerve cells from communicating with one another, leading to a host of neurological symptoms including loss of sensation, muscle spasms and weakness, fatigue, and pain. Multiple sclerosis is estimated to affect about half a million people in the United States alone, with rates of diagnosis rapidly increasing. There is currently no cure for MS.

Although the cause of MS is unknown, microorganisms seem to play some sort of role. “In the literature from clinical studies, there are papers showing that microbes affect MS,” Mazmanian says. “For example, the disease gets worse after viral infections, and bacterial infections cause an increase in MS symptoms.”

On the other hand, he concedes, “it seems counterintuitive that a microbe would be involved in a disease of the central nervous system, because these are sterile tissues.”

And yet, as Mazmanian found when he began examining the multiple sclerosis literature, the suggestion of a link between bacteria and the disease is more than anecdotal. Notably, back in 1993, Caltech biochemist Leroy Hood — who was then at the University of Washington — published a paper describing a genetically engineered strain of mouse that developed a lab-induced form of multiple sclerosis known as experimental autoimmune encephalomyelitis, or EAE.

When Hood’s animals were housed at Caltech, they developed the disease. But, oddly, when the mice were shipped to a cleaner biotech facility — where their resident gut bacterial populations were reduced — they didn’t get sick. The question was, why? At the time, Mazmanian says, “the authors speculated that some environmental component was modulating MS in these animals.” Just what that environmental component was, however, remained a mystery for almost two decades.

But Mazmanian — whose laboratory examines the relationships between gut microbes, both harmful and helpful, and the immune systems of their mammalian hosts — had a hunch that intestinal bacteria were the key. “As we gained an appreciation for how profoundly the gut microbiota can affect the immune system, we decided to ask if symbiotic bacteria are the missing variable in these mice with MS,” he says.

To find out, Mazmanian and his colleagues tried to induce MS in animals that were completely devoid of the microbes that normally inhabit the digestive system. “Lo and behold, these sterile animals did not get sick,” he says.

Then the researchers decided to see what would happen if bacteria were reintroduced to the germ-free mice. But not just any bacteria. They inoculated mice with one specific organism, an unculturable bug from a group known as segmented filamentous bacteria. In prior studies, these bacteria had been shown to lead to intestinal inflammation and, more intriguingly, to induce in the gut the appearance of a particular immune-system cell known as Th17. Th17 cells are a type of T helper cell — cells that help activate and direct other immune system cells. Furthermore, Th17 cells induce the inflammatory cascade that leads to multiple sclerosis in animals.

“The question was, if this organism is inducing Th17 cells in the gut, will it be able to do so in the brain and central nervous system?” Mazmanian says. “Furthermore, with that one organism, can we restore to sterile animals the entire inflammatory response normally seen in animals with hundreds of species of gut bacteria?”

The answer? Yes on all counts. Giving the formerly germ-free mice a dose of one species of segmented filamentous bacteria induced Th17 not only in the gut but in the central nervous system and brain — and caused the formerly healthy mice to become ill with MS-like symptoms.

“It definitely shows that gut microbes have a strong role in MS, because the genetics of the animals were the same. In fact, everything was the same except for the presence of those otherwise benign bacteria, which are clearly playing a role in shaping the immune system,” Mazmanian says. “This study shows for the first time that specific intestinal bacteria have a significant role in affecting the nervous system during MS — and they do so from the gut, an anatomical location very, very far from the brain.”

Mazmanian and his colleagues don’t, however, suggest that gut bacteria are the direct cause of multiple sclerosis, which is known to be genetically linked. Rather, the bacteria may be helping to shape the immune system’s inflammatory response, thus creating conditions that could allow the disease to develop. Indeed, multiple sclerosis also has a strong environmental component; identical twins, who possess the same genome and share all of their genes, only have a 25 percent chance of sharing the disease. “We would like to suggest that gut bacteria may be the missing environmental component,” he says.

For their part, Th17 cells are needed for the immune system to properly combat infection. Problems only arise when the cells are activated in the absence of infection — just as disease can arise, Mazmanian and others suspect, when the species composition of gut bacteria become imbalanced, say, by changes in diet, because of improved hygiene (which kills off the beneficial bacteria as well as the dangerous ones), or because of stress or antibiotic use. One impact of the dysregulation of normal gut bacterial populations — a phenomenon dubbed “dysbiosis” — may be the rising rate of multiple sclerosis seen in recent years in more hygienic societies.

“As we live cleaner, we’re not just changing our exposure to infectious agents, but we’re changing our relationship with the entire microbial world, both around and inside us, and we may be altering the balance between pro- and anti-inflammatory bacteria,” leading to diseases like MS, Mazmanian says. “Perhaps treatments for diseases such as multiple sclerosis may someday include probiotic bacteria that can restore normal immune function in the gut… and the brain.”

The work was supported by funding from the California Institute of Technology, the Weston Havens Foundation, and the Edward Mallinckrodt, Jr. Foundation.

Sourced & published by Henry Sapiecha